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Alomari O, Mokresh ME, Hamam M, Teker AU, Caliskan CS, Sadigova S, Ertan SN, Wojtara M, Filinte G. Combined Stromal Vascular Fraction and Fractional CO2 Laser Therapy for Hypertrophic Scar Treatment: A Systematic Review and Meta-Analysis. Aesthetic Plast Surg 2025; 49:885-896. [PMID: 39333369 DOI: 10.1007/s00266-024-04359-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2024] [Accepted: 09/03/2024] [Indexed: 09/29/2024]
Abstract
BACKGROUND Hypertrophic scars (HTSs) result from aberrant wound healing processes, leading to raised, thickened tissue with functional discomfort and cosmetic concerns. Current treatments, including corticosteroid injections and laser therapy, have limitations. Stromal vascular fraction (SVF) therapy and CO2 laser treatment offer promising avenues, with SVF therapy showing regenerative potential and CO2 laser therapy promoting precise tissue removal and wound healing. This study aims to investigate the combined application of SVF therapy and CO2 laser treatment for HTS, aiming to enhance treatment efficacy, tissue remodeling, and aesthetic outcomes, ultimately improving patient satisfaction in HTS management. METHOD PubMed, Scopus, Embase, and Web of Science databases have been searched for relevant studies. The "R" software (version 4.3.1) along with the "tidyverse" and "meta" statistical packages utilized to analyze data related to the efficiency of this combined method. A random-effects model was fitted to the data. For each study, continuous outcomes were pooled by calculating the standardized mean difference, along with their 95% confidence intervals. The assessment of heterogeneity utilized the I2 and chi-squared tests, applying the random effect model. RESULTS Six articles fulfilled our inclusion criteria and were included in our review. Results from the pooled analysis of Vancouver Scar Scale (VSS) scores across three included studies indicated a significant impact of the SVF+CO2 method on VSS scores post-treatment (SMD=-3.0144; 95% CI:-4.3706 to -1.6583, p<0.0001). However, analysis of transepidermal water loss levels before and after treatment showed no significant difference (SMD=-2.7603; 95% CI: -6.8729 to 1.3522; p=0.1883). Comparatively, in a pooled analysis of two studies, the combined SVF+CO2 method demonstrated superior efficacy in VSS scores compared to other methods (SMD= -1.3573; 95% CI: -2.2475 to -0.4672, p = 0.0028), with moderate heterogeneity across studies (I^2=23.0%, p = 0.2545). CONCLUSION The combined application of SVF and CO2 laser treatment shows significant promise in improving hypertrophic scars' appearance and texture. The SVF+CO2 method demonstrates superior efficacy compared to other modalities, suggesting its potential as a valuable therapeutic approach for hypertrophic scar management. LEVEL OF EVIDENCE III This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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Affiliation(s)
- Omar Alomari
- Hamidiye International Faculty of Medicines, Hamidiye International School of Medicine, University of Health Sciences, 3400, 34668, Istanbul, Turkey.
| | - Muhammed Edib Mokresh
- Hamidiye International Faculty of Medicines, Hamidiye International School of Medicine, University of Health Sciences, 3400, 34668, Istanbul, Turkey
| | - Meryem Hamam
- Hamidiye International Faculty of Medicines, Hamidiye International School of Medicine, University of Health Sciences, 3400, 34668, Istanbul, Turkey
| | - Asude Ukba Teker
- Hamidiye International Faculty of Medicines, Hamidiye International School of Medicine, University of Health Sciences, 3400, 34668, Istanbul, Turkey
| | - Cagla Sumeyye Caliskan
- Hamidiye International Faculty of Medicines, Hamidiye International School of Medicine, University of Health Sciences, 3400, 34668, Istanbul, Turkey
| | - Seljan Sadigova
- Hamidiye International Faculty of Medicines, Hamidiye International School of Medicine, University of Health Sciences, 3400, 34668, Istanbul, Turkey
| | - Sinem Nur Ertan
- Hamidiye International Faculty of Medicines, Hamidiye International School of Medicine, University of Health Sciences, 3400, 34668, Istanbul, Turkey
| | - Magda Wojtara
- Department of Human Genetics, University of Michigan Medical School, Ann Arbor, USA
| | - Gaye Filinte
- Department of Plastic, Reconstructive and Aesthetic Surgery, Dr. Lutfi Kirdar Kartal Training and Research Hospital, Istanbul, Turkey
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Tang XL, Wysoczynski M, Gumpert AM, Solanki M, Li Y, Wu WJ, Zheng S, Ruble H, Li H, Stowers H, Zheng S, Ou Q, Tanveer N, Slezak J, Kalra DK, Bolli R. Intravenous infusions of mesenchymal stromal cells have cumulative beneficial effects in a porcine model of chronic ischaemic cardiomyopathy. Cardiovasc Res 2024; 120:1939-1952. [PMID: 39163570 PMCID: PMC11630033 DOI: 10.1093/cvr/cvae173] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2024] [Revised: 07/08/2024] [Accepted: 07/23/2024] [Indexed: 08/22/2024] Open
Abstract
AIMS The development of cell therapy as a widely available clinical option for ischaemic cardiomyopathy is hindered by the invasive nature of current cell delivery methods. Furthermore, the rapid disappearance of cells after transplantation provides a cogent rationale for using repeated cell doses, which, however, has not been done thus far in clinical trials because it is not feasible with invasive approaches. The goal of this translational study was to test the therapeutic utility of the intravenous route for cell delivery. METHODS AND RESULTS Pigs with chronic ischaemic cardiomyopathy induced by myocardial infarction received one or three intravenous doses of allogeneic bone marrow mesenchymal stromal cells (MSCs) or placebo 35 days apart. Rigour guidelines, including blinding and randomization, were strictly followed. A comprehensive assessment of left ventricular (LV) function was conducted with three independent methods (echocardiography, magnetic resonance imaging, and haemodynamic studies). The results demonstrate that three doses of MSCs improved both load-dependent and independent indices of LV function and reduced myocardial hypertrophy and fibrosis; in contrast, one dose failed to produce most of these benefits. CONCLUSIONS To our knowledge, this is the first study to show that intravenous infusion of a cell product improves LV function and structure in a large animal model of chronic ischaemic cardiomyopathy and that repeated infusions are necessary to produce robust effects. This study, conducted in a clinically relevant model, supports a new therapeutic strategy based on repeated intravenous infusions of allogeneic MSCs and provides a foundation for a first-in-human trial testing this strategy in patients with chronic ischaemic cardiomyopathy.
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Affiliation(s)
- Xian-Liang Tang
- Institute of Molecular Cardiology, University of Louisville, 550 S Jackson Street, ACB Bldg, 3rd Floor, Louisville, KY 40202
| | - Marcin Wysoczynski
- Institute of Molecular Cardiology, University of Louisville, 550 S Jackson Street, ACB Bldg, 3rd Floor, Louisville, KY 40202
| | - Anna M Gumpert
- Institute of Molecular Cardiology, University of Louisville, 550 S Jackson Street, ACB Bldg, 3rd Floor, Louisville, KY 40202
| | - Mitesh Solanki
- Institute of Molecular Cardiology, University of Louisville, 550 S Jackson Street, ACB Bldg, 3rd Floor, Louisville, KY 40202
| | - Yan Li
- Institute of Molecular Cardiology, University of Louisville, 550 S Jackson Street, ACB Bldg, 3rd Floor, Louisville, KY 40202
| | - Wen-Jian Wu
- Institute of Molecular Cardiology, University of Louisville, 550 S Jackson Street, ACB Bldg, 3rd Floor, Louisville, KY 40202
| | - Shirong Zheng
- Institute of Molecular Cardiology, University of Louisville, 550 S Jackson Street, ACB Bldg, 3rd Floor, Louisville, KY 40202
| | - Halina Ruble
- Institute of Molecular Cardiology, University of Louisville, 550 S Jackson Street, ACB Bldg, 3rd Floor, Louisville, KY 40202
| | - Hong Li
- Institute of Molecular Cardiology, University of Louisville, 550 S Jackson Street, ACB Bldg, 3rd Floor, Louisville, KY 40202
| | - Heather Stowers
- Institute of Molecular Cardiology, University of Louisville, 550 S Jackson Street, ACB Bldg, 3rd Floor, Louisville, KY 40202
| | - Shengnan Zheng
- Institute of Molecular Cardiology, University of Louisville, 550 S Jackson Street, ACB Bldg, 3rd Floor, Louisville, KY 40202
| | - Qinghui Ou
- Institute of Molecular Cardiology, University of Louisville, 550 S Jackson Street, ACB Bldg, 3rd Floor, Louisville, KY 40202
| | - Nida Tanveer
- Institute of Molecular Cardiology, University of Louisville, 550 S Jackson Street, ACB Bldg, 3rd Floor, Louisville, KY 40202
| | - Jan Slezak
- Centre of Experimental Medicine, Institute for Heart Research, Bratislava, Slovakia
| | - Dinesh K Kalra
- Institute of Molecular Cardiology, University of Louisville, 550 S Jackson Street, ACB Bldg, 3rd Floor, Louisville, KY 40202
| | - Roberto Bolli
- Institute of Molecular Cardiology, University of Louisville, 550 S Jackson Street, ACB Bldg, 3rd Floor, Louisville, KY 40202
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Onoi Y, Matsumoto T, Anjiki K, Hayashi S, Nakano N, Kuroda Y, Tsubosaka M, Kamenaga T, Ikuta K, Tachibana S, Suda Y, Wada K, Maeda T, Saitoh A, Hiranaka T, Sobajima S, Iwaguro H, Matsushita T, Kuroda R. Human uncultured adipose-derived stromal vascular fraction shows therapeutic potential against osteoarthritis in immunodeficient rats via direct effects of transplanted M2 macrophages. Stem Cell Res Ther 2024; 15:325. [PMID: 39334434 PMCID: PMC11438128 DOI: 10.1186/s13287-024-03946-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2024] [Accepted: 09/18/2024] [Indexed: 09/30/2024] Open
Abstract
BACKGROUND The uncultured adipose-derived stromal vascular fraction (SVF), consisting of adipose-derived stromal cells (ADSCs), M2 macrophages (M2Φ) and others, has shown therapeutic potential against osteoarthritis (OA), however, the mechanisms underlying its therapeutic effects remain unclear. Therefore, this study investigated the effects of the SVF on OA in a human-immunodeficient rat xenotransplantation model. METHODS OA model was induced in the knees of female immunodeficient rats by destabilization of the medial meniscus. Immediately after the surgery, human SVF (1 × 105), ADSCs (1 × 104), or phosphate buffered saline as a control group were transplanted into the knees. At 4 and 8 weeks postoperatively, OA progression and synovitis were analyzed by macroscopic and histological analyses, and the expression of collagen II, SOX9, MMP-13, ADAMTS-5, F4/80, CD86 (M1), CD163 (M2), and human nuclear antigen (hNA) were evaluated immunohistochemically. In vitro, flow cytometry was performed to collect CD163-positive cells as M2Φ from the SVF. Chondrocyte pellets (1 × 105) were co-cultured with SVF (1 × 105), M2Φ (1 × 104), and ADSCs (1 × 104) or alone as a control group, and the pellet size was compared. TGF-β, IL-10 and MMP-13 concentrations in the medium were evaluated using enzyme-linked immunosorbent assay. RESULTS In comparison with the control and ADSC groups, the SVF group showed significantly slower OA progression and less synovitis with higher expression of collagen II and SOX9, lower expression of MMP-13 and ADAMTS-5, and lower F4/80 and M1/M2 ratio in the synovium. Only the SVF group showed partial expression of hNA-, CD163-, and F4/80-positive cells in the rat synovium. In vitro, the SVF, M2Φ, ADSC and control groups, in that order, showed larger pellet sizes, higher TGF-β and IL-10, and lower MMP-13 concentrations. CONCLUSIONS The M2Φ in the transplanted SVF directly affected recipient tissue, enhancing the secretion of growth factors and chondrocyte-protecting cytokines, and partially improving chondrocytes and joint homeostasis. These findings indicate that the SVF is as an effective option for regenerative therapy for OA, with mechanisms different from those of ADSCs.
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Affiliation(s)
- Yuma Onoi
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Tomoyuki Matsumoto
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
| | - Kensuke Anjiki
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Shinya Hayashi
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Naoki Nakano
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Yuichi Kuroda
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Masanori Tsubosaka
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Tomoyuki Kamenaga
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Kemmei Ikuta
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Shotaro Tachibana
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Yoshihito Suda
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Kensuke Wada
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Takuma Maeda
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Akira Saitoh
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Takafumi Hiranaka
- Department of Orthopaedic Surgery and Joint Surgery Center, Takatsuki General Hospital, Osaka, Japan
| | - Satoshi Sobajima
- Department of Orthopaedic Surgery, Sobajima Clinic, Osaka, Japan
| | - Hideki Iwaguro
- Department of Orthopaedic Surgery, Sobajima Clinic, Osaka, Japan
| | - Takehiko Matsushita
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Ryosuke Kuroda
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
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Jović D, Preradović L, Jović F, Kremenović M, Lukić D, Antonić M, Unčanin N, Jović M. Optimizing adipose-derived stromal vascular fraction storage: Temperature and time impact on cell viability in regenerative medicine. Medicine (Baltimore) 2024; 103:e39859. [PMID: 39312305 PMCID: PMC11419534 DOI: 10.1097/md.0000000000039859] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Accepted: 09/06/2024] [Indexed: 09/25/2024] Open
Abstract
BACKGROUND The adipose-derived stromal vascular fraction (SVF) plays a crucial role in regenerative medicine owing to its regenerative and immunomodulatory properties. However, the effective utilization of SVF in therapeutic applications requires careful consideration of storage conditions to maintain cell viability. METHODS We conducted a research on 43 patients of different ages and sexes who were older than 18 years. This study explored the impact of different temperatures (-80, -20, and 4 °C) on SVF storage in platelet-poor plasma for 1 and 6 months. SVF extracted using a semi-UNISTATION™ system was subjected to rigorous analysis of cell count and viability using a LUNA-STEM™ Dual Fluorescence Cell Counter. RESULTS The results indicated a significant correlation between the storage conditions and SVF viability. Notably, storing SVF at 4 °C demonstrated the highest cell viability and count, while -80 °C storage exhibited the least favorable outcomes. This study emphasizes the importance of minimizing storage time to preserve SVF viability, as evidenced by a decline in both cell count and viability over a 6-month period. Comparisons with the existing literature underscore the need for precise protocols for SVF storage, with considerations for temperature and cryoprotective agents. These findings provide valuable insights for developing optimal SVF storage protocols to enhance therapeutic outcomes and reduce the need for repeated adipose tissue harvesting. Despite the limitations of the study, such as the use of a cell counter instead of flow cytometry, the results establish the foundation for further research on refining SVF storage methods. CONCLUSION The ideal storage temperature is from 4 °C, while the length of storage time inversely affects the viability of SVF; the longer the storage time, the lower the number and the viability of SVF cells, regardless of the temperature at which they are preserved.
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Affiliation(s)
- Darko Jović
- University of Banja Luka, Faculty of Medicine, Banja Luka, Bosnia and Herzegovina
- Special Hospital S-tetik, Banja Luka, Bosnia and Herzegovina
| | - Ljubiša Preradović
- University of Banja Luka, Faculty of Medicine, Banja Luka, Bosnia and Herzegovina
| | - Filip Jović
- University of Ulm, Faculty of Medicine, Ulm, Germany
| | - Mićo Kremenović
- Special Hospital S-tetik, Banja Luka, Bosnia and Herzegovina
| | - Darko Lukić
- University of Banja Luka, Faculty of Medicine, Banja Luka, Bosnia and Herzegovina
| | - Milica Antonić
- Special Hospital S-tetik, Banja Luka, Bosnia and Herzegovina
| | - Nikola Unčanin
- University Clinical Centre of the Republic of Srpska, Banja Luka, Bosnia and Herzegovina
| | - Matija Jović
- University of Belgrade, Faculty of Medicine, Belgrade, Serbia
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Korn A, Simsek S, Fiet MD, Waas IS, Niessen HW, Krijnen PA. Application of adipose tissue-derived stem cell therapy with a clinically relevant dose does not significantly affect atherosclerotic plaque characteristics in a streptozotocin-induced hyperglycaemia mouse model. JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY PLUS 2024; 9:100083. [PMID: 39803590 PMCID: PMC11708420 DOI: 10.1016/j.jmccpl.2024.100083] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 05/27/2024] [Accepted: 07/08/2024] [Indexed: 01/16/2025]
Abstract
Aims Diabetes mellitus (DM) induces increased inflammation of atherosclerotic plaques, resulting in elevated plaque instability. Mesenchymal stem cell (MSC) therapy was shown to decrease plaque size and increase stability in non-DM animal models. We now studied the effect of MSC therapy in a streptozotocin-induced hyperglycaemia mouse model using a clinically relevant dose of adipose tissue-derived MSCs (ASCs). Methods Hyperglycaemia was induced in male C57BL/6 ApoE-/- mice (n=24) via intraperitoneal streptozotocin (STZ) injection (0.05 mg/g bodyweight) for 5 consecutive days. 16 weeks after the first STZ injection, the mice received either 100,000 ASCs (n=9) or vehicle (n=14) intravenously. The effects of ASC treatment on the size and stability of aortic root atherosclerotic plaques were determined 4 weeks post-treatment via (immuno)histochemical analyses. Furthermore, plasma monocyte subsets within 3 days pre- and 3 days post-treatment, and 4 weeks post-treatment, were studied. Results ASC treatment did not significantly affect atherosclerotic plaque size or intra-plaque inflammation. Although ASC-treated mice had a higher percentage of intra-plaque fibrosis (42.5±3.3%) compared to vehicle-treated mice (37.6±6.8%, p=0.07), this did not reach significance. Additionally, although differences in the percentages of circulating pro- and anti-inflammatory monocytes were observed after ASC treatment compared to pre-treatment (p=0.005), their levels did not differ significantly at any time point compared to vehicle-treated mice. Conclusions ASC treatment with a clinically relevant dose did not significantly affect atherosclerotic plaque size or intra-plaque inflammation in a hyperglycaemia mouse model. Despite a borderline significant improvement in intraplaque fibrotic content, the potential of ASC treatment on atherosclerotic plaque stability in a diabetic environment remains to be determined.
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Affiliation(s)
- Amber Korn
- Department of Pathology, Amsterdam University Medical Centres (AUMC), Location VUmc, Amsterdam, the Netherlands
- Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands
| | - Suat Simsek
- Department of Internal Medicine, Northwest Clinics, Alkmaar, the Netherlands
- Department of Internal Medicine, AUMC, Location VUmc, Amsterdam, the Netherlands
| | - Mitchell D. Fiet
- Department of Pathology, Amsterdam University Medical Centres (AUMC), Location VUmc, Amsterdam, the Netherlands
- Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands
| | | | - Hans W.M. Niessen
- Department of Pathology, Amsterdam University Medical Centres (AUMC), Location VUmc, Amsterdam, the Netherlands
- Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands
- Department of Cardiac Surgery, AUMC, Location VUmc, Amsterdam, the Netherlands
| | - Paul A.J. Krijnen
- Department of Pathology, Amsterdam University Medical Centres (AUMC), Location VUmc, Amsterdam, the Netherlands
- Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands
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Aglan HA, Ahmed HH, Beherei HH, Abdel-Hady BM, Ekram B, Kishta MS. Generation of cardiomyocytes from stem cells cultured on nanofibrous scaffold: Experimental approach for attenuation of myocardial infarction. Tissue Cell 2024; 89:102461. [PMID: 38991272 DOI: 10.1016/j.tice.2024.102461] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Revised: 06/04/2024] [Accepted: 07/01/2024] [Indexed: 07/13/2024]
Abstract
The current study was constructed to fabricate polyamide based nanofibrous scaffolds (NS) and to define the most promising one for the generation of cardiomyocytes from adipose tissue derived mesenchymal stem cells (ADMSCs). This purpose was extended to assess the potentiality of the generated cardiomyocytes in relieving myocardial infarction (MI) in rats. Production and characterization of NSs were carried out. ADMSCs were cultured on NS and induced to differentiate into cardiomyocytes by specific growth factors. Molecular analysis for myocyte-specific enhancer factor 2 C (MEF2C) and alpha sarcomeric actin (α-SCA) expression was done to confirm the differentiation of ADMSCs into cardiomyocytes for further transplantation into MI induced rats. Implantation of cells in MI afflicted rats boosted heart rate, ST height and PR interval and lessened P duration, RR, QTc and QRS intervals. Also, this type of medication minified serum lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) enzymes activity as well as serum and cardiac troponin T (Tn-T) levels and upraised serum and cardiac α-SCA and cardiac connexin 43 (CX 43) levels. Microscopic feature of cardiac tissue sections of rats in the treated groups revealed great renovation in the cardiac microarchitecture. Conclusively, this attempt gains insight into a realistic strategy for recovery of MI through systemic employment of in vitro generated cardiomyocytes.
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Affiliation(s)
- Hadeer A Aglan
- Hormones Department, Medical Research and Clinical Studies Institute, National Research Centre, Giza, Egypt; Stem Cell Lab., Center of Excellence for Advanced Sciences, National Research Centre, Giza, Egypt.
| | - Hanaa H Ahmed
- Hormones Department, Medical Research and Clinical Studies Institute, National Research Centre, Giza, Egypt; Stem Cell Lab., Center of Excellence for Advanced Sciences, National Research Centre, Giza, Egypt
| | - Hanan H Beherei
- Refractories, Ceramics and Building Materials Department, Advanced Materials Technology and Mineral Resources Research Institute, National Research Centre, Giza, Egypt
| | - Bothaina M Abdel-Hady
- Polymers and Pigments Department, Chemical Industries Institute, National Research Centre, Giza, Egypt
| | - Basma Ekram
- Polymers and Pigments Department, Chemical Industries Institute, National Research Centre, Giza, Egypt
| | - Mohamed S Kishta
- Hormones Department, Medical Research and Clinical Studies Institute, National Research Centre, Giza, Egypt; Stem Cell Lab., Center of Excellence for Advanced Sciences, National Research Centre, Giza, Egypt
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Dong Y, Huang Y, Hou T, Li P. Effectiveness and Safety of Different Methods of Assisted Fat Grafting: A Network Meta-Analysis. Aesthetic Plast Surg 2024; 48:2484-2499. [PMID: 38772943 DOI: 10.1007/s00266-024-04060-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Accepted: 04/09/2024] [Indexed: 05/23/2024]
Abstract
OBJECTIVE Numerous studies have proposed the utilization of stromal vascular fraction (SVF), adipose-derived stem cells (ADSCs), and platelet products as auxiliary grafting techniques to improve the survival rate of fat grafts. This study aimed to evaluate the efficacy and safety of various fat grafting methods since 2010 through a network meta-analysis, aiming to identify the most effective technique for fat grafting. METHODS Clinic trials on assisted fat grafting were searched from Pubmed, Embase, Web of Science, and the Cochrane Library, spanning the period from January 1, 2010 to March 2024. The risk of bias in the included trials was meticulously assessed using the Cochrane risk of bias tool. The survival rate of fat grafts served as the primary evaluation metric for effectiveness, while complications were employed as the indicator for safety. RESULTS The study incorporated 31 clinic trials, involving a total of 1656 patients. The findings indicated that the survival rate with assisted fat grafting significantly surpassed that of simple fat grafting (SUCRA, 10.43%). Notably, ADSC-assisted fat grafting exhibited the highest survival rate (SUCRA, 82.17%), followed by Salvia miltiorrhiza (SM)-assisted fat grafting (SUCRA, 69.76%). In terms of safety, the most prevalent complications associated with fat grafting were fat sclerosis and fat necrosis. Adc-assisted fat grafting was correlated with the lowest incidence of complications (SUCRA, 41.00%), followed by simple fat grafting (SUCRA, 40.99%). However, PRP-assisted (SUCRA, 52.86%) and SVF-assisted fat grafting (SUCRA, 65.14%) showed higher complication rates. CONCLUSION Various methods of assisted fat grafting can significantly enhance the survival rate, but they often fail to effectively mitigate the incidence of complications. Compared to other methods, adipose mesenchymal stem cells-assisted fat grafting consistently yielded a higher survival rate of grafts and fewer complications. Consequently, this approach represents a relatively effective method for assisting in fat grafting at present. LEVEL OF EVIDENCE III This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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Affiliation(s)
- Yue Dong
- Department of Burn and Plastic Surgery-Department of Medical Cosmetology, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, 225000, Yangzhou, Jiangsu Province, China
- Clinical Medical College, Yangzhou University, 225000, Yangzhou, Jiangsu Province, China
| | - Yanling Huang
- Department of Burn and Plastic Surgery-Department of Medical Cosmetology, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, 225000, Yangzhou, Jiangsu Province, China
- Clinical Medical College, Yangzhou University, 225000, Yangzhou, Jiangsu Province, China
| | - Tuanjie Hou
- Department of Burn and Plastic Surgery-Department of Medical Cosmetology, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, 225000, Yangzhou, Jiangsu Province, China.
- Clinical Medical College, Yangzhou University, 225000, Yangzhou, Jiangsu Province, China.
| | - Pingsong Li
- Department of Burn and Plastic Surgery-Department of Medical Cosmetology, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, 225000, Yangzhou, Jiangsu Province, China.
- Clinical Medical College, Yangzhou University, 225000, Yangzhou, Jiangsu Province, China.
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Gareev I, Beylerli O, Ilyasova T, Ahmad A, Shi H, Chekhonin V. Therapeutic application of adipose-derived stromal vascular fraction in myocardial infarction. iScience 2024; 27:109791. [PMID: 38736548 PMCID: PMC11088339 DOI: 10.1016/j.isci.2024.109791] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/14/2024] Open
Abstract
The insufficiency of natural regeneration processes in higher organisms, including humans, underlies myocardial infarction (MI), which is one of the main causes of disability and mortality in the population of developed countries. The solution to this problem lies in the field of revealing the mechanisms of regeneration and creating on this basis new technologies for stimulating endogenous regenerative processes or replacing lost parts of tissues and organs with transplanted cells. Of great interest is the use of the so-called stromal vascular fraction (SVF), derived from autologous adipose tissue. It is known that the main functions of SVF are angiogenetic, antiapoptotic, antifibrotic, immune regulation, anti-inflammatory, and trophic. This study presents data on the possibility of using SVF, targeted regulation of its properties and reparative potential, as well as the results of research studies on its use for the restoration of damaged ischemic tissue after MI.
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Affiliation(s)
- Ilgiz Gareev
- Bashkir State Medical University, Ufa 450008, Russian Federation
| | - Ozal Beylerli
- Bashkir State Medical University, Ufa 450008, Russian Federation
| | - Tatiana Ilyasova
- Bashkir State Medical University, Ufa 450008, Russian Federation
| | - Aamir Ahmad
- Translational Research Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar
| | - Huaizhang Shi
- Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin 1500, China
| | - Vladimir Chekhonin
- Pirogov Russian National Research Medical University of the Ministry of Healthcare of Russian Federation, Moscow, Russian Federation
- Serbsky Federal Medical Research Centre of Psychiatry and Narcology of the Ministry of Healthcare of Russian Federation, Moscow, Russian Federation
- The National Medical Research Center for Endocrinology, Moscow, Russian Federation
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9
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Zhang Y, Zhang Y, Hu A, Meng F, Cui P, Li T, Cui G. Mesenchymal stem cells derived from CHIR99021 and TGF‑β induction remained on the colicomentum and improved cardiac function of a rat model of acute myocardium infarction. Exp Ther Med 2024; 27:182. [PMID: 38515646 PMCID: PMC10952379 DOI: 10.3892/etm.2024.12470] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2023] [Accepted: 01/17/2024] [Indexed: 03/23/2024] Open
Abstract
Human induced pluripotent stem cells (hiPSCs) have been regarded as a potential stem cell source for cell therapy. However, the production of cells with mesenchymal potential from hiPSCs through spontaneous differentiation is time consuming and laborious. In the present study, the combined use of the GSK-3 inhibitor CHIR99021 and TGF-β was used to obtain mesenchymal stem cell (MSC)-like cells from hiPSCs. During the induction process, the transcription of epithelial-mesenchymal transition (EMT)-related genes N-cadherin and Vimentin in the transformed cells was upregulated, whereas the transcription of E-cadherin and pluripotency-related transcription factors SOX2, OCT4 and NANOG did not change significantly. This indicated that whilst cells were pluripotent, EMT was initiated by the upregulation of transcription of EMT promoting genes. Both SMAD-dependent and independent signalling pathways were significantly activated by the combined induction treatment compared with the single factor induction. The hiPSC-derived MSC-like cells (hiPSC-MSCs) expressed MSC-related markers and acquired osteogenic, chondrogenic and adipogenic differentiation potentials. After being injected into the peritoneal cavity of rats, the hiPSC-MSCs secreted angiogenic and immune-regulatory factors and remained on the colicomentum for 3 weeks. Within an 11-week period, four intraperitoneal hiPSC-MSC injections (1x107 cells/injection) into acute myocardial infarction (AMI) model rats significantly increased the left ventricular ejection fraction, left ventricular fractional shortening and angiogenesis and significantly reduced scar size and the extent of apoptosis in the infarcted area compared with that of the control PBS injection. Symptoms of hiPSC-MSC-induced immune reaction or tumour formation were not observed over the course of the experiment in the hiSPC-MSC treated rats. In conclusion, the CHIR99021 and TGF-β combined induction was a rapid and effective method to obtain MSC-like cells from hiPSCs and multiple high dose intraperitoneal injections of hiPSC-derived MSCs were safe and effective at restoring cardiac function in an AMI rat model.
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Affiliation(s)
- Yusen Zhang
- Department of Ultrasound, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China
| | - Yanmin Zhang
- Central Laboratory, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China
| | - Azhen Hu
- Shenzhen Key Laboratory of Drug Addiction and Safe Medication, Shenzhen PKU-HKUST Medical Centre, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China
| | - Fanhua Meng
- Reproductive Medical Centre, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China
| | - Peng Cui
- Institute of Precision Medicine, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China
| | - Tianshi Li
- Department of Plastic Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China
| | - Guanghui Cui
- Central Laboratory, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China
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10
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Erçelik O, Karadaş H, Kaptan Z, Bilgen AS, Samaraz Olgun P, Çaydere M, Hücümenoğlu S. The effect of adipose tissue-derived stromal vascular fraction/gel material on wound healing in a rat model of nasal mucosa injury. Acta Otolaryngol 2024; 144:371-378. [PMID: 39141586 DOI: 10.1080/00016489.2024.2385594] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2024] [Revised: 07/16/2024] [Accepted: 07/17/2024] [Indexed: 08/16/2024]
Abstract
BACKGROUND Stromal Vascular fraction/gel (SVF/gel) is prepared mechanically from autologous adipose tissue, and it is known for its regenerative and anti-inflammatory properties. AIMS To assess histopathological effects of adipose tissue-derived SVF/gel and nasal steroids on nasal mucosal healing. MATERIAL AND METHODS Forty-two Wistar Albino rats with right nasal mucosal injury were randomly divided into three groups: control (saline), Mometasone Furoate (MF), and SVF/gel. Control group (n = 14) received saline for 7 days, while MF group (n = 14) was administered MF to the right nasal cavity for 7 days. SVF/gel group (n = 14) was treated once with SVF/gel in the right nasal cavity. Histological analysis on days 14 and 28 post-injury focused on evaluating epithelial thickness, inflammation, disarray, subepithelial thickness, goblet cell count, subepithelial fibrosis, presence of ciliated cells, lacunae, adhesion, and neo-osteogenesis. RESULTS When comparing the MF and SVF/gel groups, statistically significant differences were found on day 14 in indices of epithelial thickness, subepithelial thickness, goblet cells, subepithelial fibrosis, and ciliated cells. On day 28, SVF/gel group exhibited higher ciliated cell counts and lower subepithelial fibrosis values (p = .027; p = .016). Additionally, epithelial disarray, adhesions, lacunae, and neo-osteogenesis were not observed in the SVF/gel group. CONCLUSIONS AND SIGNIFICANCE SVF/gel accelerates re-epithelialization, reduces fibrosis and adhesions, and enhances cilia formation compared to nasal steroids. These findings suggest that SVF/gel is an autologous and cost-effective treatment for improving nasal mucosal healing post-injury.
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Affiliation(s)
- Onur Erçelik
- Department of Otolaryngology-Head and Neck Surgery, Bandırma State Hospital, Bandırma, Balıkesir, Turkey
| | - Hatice Karadaş
- Department of Otolaryngology-Head and Neck Surgery, Ankara Research and Training Hospital, Ankara, Turkey
| | - Zeynep Kaptan
- Department of Otolaryngology-Head and Neck Surgery, Ankara Research and Training Hospital, Ankara, Turkey
| | - Akif Sinan Bilgen
- Department of Otolaryngology-Head and Neck Surgery, Ankara Research and Training Hospital, Ankara, Turkey
| | - Pelin Samaraz Olgun
- Department of Otolaryngology-Head and Neck Surgery, Kırşehir Research and Training Hospital, Kırşehir, Turkey
| | - Muzaffer Çaydere
- Department of Pathology, Ankara Research and Training Hospital, Ankara, Turkey
| | - Sema Hücümenoğlu
- Department of Pathology, Ankara Research and Training Hospital, Ankara, Turkey
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11
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Ertlen C, Seblani M, Bonnet M, Brezun JM, Coyle T, Sabatier F, Fuentes S, Decherchi P, Serratrice N, Marqueste T. Efficacy of the immediate adipose-derived stromal vascular fraction autograft on functional sensorimotor recovery after spinal cord contusion in rats. Stem Cell Res Ther 2024; 15:29. [PMID: 38303017 PMCID: PMC10835949 DOI: 10.1186/s13287-024-03645-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2023] [Accepted: 01/23/2024] [Indexed: 02/03/2024] Open
Abstract
BACKGROUND Spinal cord injuries (SCI) lead to functional alteration with important consequences such as motor and sensory disorders. The repair strategies developed to date remain ineffective. The adipose tissue-derived stromal vascular fraction (SVF) is composed of a cocktail of cells with trophic, pro-angiogenic and immunomodulatory effects. Numerous therapeutic benefits were shown for tissue reconstitution, peripheral neuropathy and for the improvement of neurodegenerative diseases. Here, the therapeutic efficacy of SVF on sensorimotor recovery after an acute thoracic spinal cord contusion in adult rats was determined. METHOD Male Sprague Dawley rats (n = 45) were divided into 3 groups: SHAM (without SCI and treatment), NaCl (animals with a spinal lesion and receiving a saline injection through the dura mater) and SVF (animals with a spinal lesion and receiving a fraction of fat removed from adipocytes through the dura mater). Some animals were sacrificed 14 days after the start of the experiment to determine the inflammatory reaction by measuring the interleukin-1β, interleukin-6 and Tumor Necrosis Factor-α in the lesion area. Other animals were followed once a week for 12 weeks to assess functional recovery (postural and locomotor activities, sensorimotor coordination). At the end of this period, spinal reflexivity (rate-dependent depression of the H-reflex) and physiological adjustments (ventilatory response to metabosensitive muscle activation following muscle fatigue) were measured with electrophysiological tools. RESULTS Compared to non-treated animals, results indicated that the SVF reduced the endogenous inflammation and increased the behavioral recovery in treated animals. Moreover, H-reflex depression and ventilatory adjustments to muscle fatigue were found to be comparable between SHAM and SVF groups. CONCLUSION Our results highlight the effectiveness of SVF and its high therapeutic potential to improve sensorimotor functions and to restore the segmental sensorimotor loop and the communication between supra- and sub-lesional spinal cord regions after traumatic contusion.
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Affiliation(s)
- Céline Ertlen
- Aix-Marseille Univ, CNRS, ISM UMR 7287, Institut des Sciences du Mouvement: Etienne-Jules MAREY, Equipe Plasticité Des Systèmes Nerveux Et Musculaire (PSNM), Parc Scientifique Et Technologique de Luminy, Aix Marseille Univ, CC910 - 163, Avenue de Luminy, 13288, Marseille Cedex 09, France
| | - Mostafa Seblani
- Aix-Marseille Univ, CNRS, ISM UMR 7287, Institut des Sciences du Mouvement: Etienne-Jules MAREY, Equipe Plasticité Des Systèmes Nerveux Et Musculaire (PSNM), Parc Scientifique Et Technologique de Luminy, Aix Marseille Univ, CC910 - 163, Avenue de Luminy, 13288, Marseille Cedex 09, France
| | - Maxime Bonnet
- Aix-Marseille Univ, CNRS, ISM UMR 7287, Institut des Sciences du Mouvement: Etienne-Jules MAREY, Equipe Plasticité Des Systèmes Nerveux Et Musculaire (PSNM), Parc Scientifique Et Technologique de Luminy, Aix Marseille Univ, CC910 - 163, Avenue de Luminy, 13288, Marseille Cedex 09, France
| | - Jean-Michel Brezun
- Aix-Marseille Univ, CNRS, ISM UMR 7287, Institut des Sciences du Mouvement: Etienne-Jules MAREY, Equipe Plasticité Des Systèmes Nerveux Et Musculaire (PSNM), Parc Scientifique Et Technologique de Luminy, Aix Marseille Univ, CC910 - 163, Avenue de Luminy, 13288, Marseille Cedex 09, France
| | - Thelma Coyle
- Aix-Marseille Univ, CNRS, ISM UMR 7287, Institut des Sciences du Mouvement: Etienne-Jules MAREY, Equipe Plasticité Des Systèmes Nerveux Et Musculaire (PSNM), Parc Scientifique Et Technologique de Luminy, Aix Marseille Univ, CC910 - 163, Avenue de Luminy, 13288, Marseille Cedex 09, France
| | - Florence Sabatier
- Assistance Publique - Hôpitaux de Marseille (AP-HM), INSERM 1409 Centre d'Investigation Clinique en Biothérapies, Unité de Culture Et Thérapie Cellulaire, Hôpital de La Conception, 147, Boulevard Baille, 13385, Marseille Cedex 05, France
| | - Stéphane Fuentes
- Assistance Publique - Hôpitaux de Marseille (AP-HM), Service de Neurochirurgie, Hôpital de La Timone, 264, Rue Saint-Pierre, 13005, Marseille, France
| | - Patrick Decherchi
- Aix-Marseille Univ, CNRS, ISM UMR 7287, Institut des Sciences du Mouvement: Etienne-Jules MAREY, Equipe Plasticité Des Systèmes Nerveux Et Musculaire (PSNM), Parc Scientifique Et Technologique de Luminy, Aix Marseille Univ, CC910 - 163, Avenue de Luminy, 13288, Marseille Cedex 09, France.
| | - Nicolas Serratrice
- Aix-Marseille Univ, CNRS, ISM UMR 7287, Institut des Sciences du Mouvement: Etienne-Jules MAREY, Equipe Plasticité Des Systèmes Nerveux Et Musculaire (PSNM), Parc Scientifique Et Technologique de Luminy, Aix Marseille Univ, CC910 - 163, Avenue de Luminy, 13288, Marseille Cedex 09, France
- Assistance Publique - Hôpitaux de Marseille (AP-HM), Service de Neurochirurgie, Hôpital de La Timone, 264, Rue Saint-Pierre, 13005, Marseille, France
| | - Tanguy Marqueste
- Aix-Marseille Univ, CNRS, ISM UMR 7287, Institut des Sciences du Mouvement: Etienne-Jules MAREY, Equipe Plasticité Des Systèmes Nerveux Et Musculaire (PSNM), Parc Scientifique Et Technologique de Luminy, Aix Marseille Univ, CC910 - 163, Avenue de Luminy, 13288, Marseille Cedex 09, France.
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12
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Sun Z, Cai Y, Chen Y, Jin Q, Zhang Z, Zhang L, Li Y, Huang L, Wang J, Yang Y, Lv Q, Han Z, Xie M, Zhu X. Ultrasound-targeted microbubble destruction promotes PDGF-primed bone mesenchymal stem cell transplantation for myocardial protection in acute Myocardial Infarction in rats. J Nanobiotechnology 2023; 21:481. [PMID: 38102643 PMCID: PMC10725038 DOI: 10.1186/s12951-023-02204-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Accepted: 11/07/2023] [Indexed: 12/17/2023] Open
Abstract
BACKGROUND Ultrasound-targeted microbubble destruction (UTMD) has emerged as a promising strategy for the targeted delivery of bone marrow mesenchymal stem cells (MSCs) to the ischemic myocardium. However, the limited migration capacity and poor survival of MSCs remains a major therapeutic barrier. The present study was performed to investigate the synergistic effect of UTMD with platelet-derived growth factor BB (PDGF-BB) on the homing of MSCs for acute myocardial infarction (AMI). METHODS MSCs from male donor rats were treated with PDGF-BB, and a novel microbubble formulation was prepared using a thin-film hydration method. In vivo, MSCs with or without PDGF-BB pretreatment were transplanted by UTMD after inducing AMI in experimental rats. The therapeutic efficacy of PDGF-BB-primed MSCs on myocardial apoptosis, angiogenesis, cardiac function and scar repair was estimated. The effects and molecular mechanisms of PDGF-BB on MSC migration and survival were explored in vitro. RESULTS The results showed that the biological effects of UTMD increased the local levels of stromal-derived factor-1 (SDF-1), which promoted the migration of transplanted MSCs to the ischemic region. Compared with UTMD alone, UTMD combined with PDGF-BB pretreatment significantly increased the cardiac homing of MSCs, which subsequently reduced myocardial apoptosis, promoted neovascularization and tissue repair, and increased cardiac function 30 days after MI. The vitro results demonstrated that PDGF-BB enhanced MSC migration and protected these cells from H2O2-induced apoptosis. Mechanistically, PDGF-BB pretreatment promoted MSC migration and inhibited H2O2-induced MSC apoptosis via activation of the phosphatidylinositol 3-kinase/serine-threonine kinase (PI3K/Akt) pathway. Furthermore, crosstalk between PDGF-BB and stromal-derived factor-1/chemokine receptor 4 (SDF-1/CXCR4) is involved in the PI3K/AKT signaling pathway. CONCLUSION The present study demonstrated that UTMD combined with PDGF-BB treatment could enhance the homing ability of MSCs, thus alleviating AMI in rats. Therefore, UTMD combined with PDGF-BB pretreatment may offer exciting therapeutic opportunities for strengthening MSC therapy in ischemic diseases.
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Grants
- 81701716; 82230066, 81922033, 81727805, 82171961, 81801715, 81801716 National Natural Science Foundation of China
- 81701716; 82230066, 81922033, 81727805, 82171961, 81801715, 81801716 National Natural Science Foundation of China
- 81701716; 82230066, 81922033, 81727805, 82171961, 81801715, 81801716 National Natural Science Foundation of China
- 81701716; 82230066, 81922033, 81727805, 82171961, 81801715, 81801716 National Natural Science Foundation of China
- 81701716; 82230066, 81922033, 81727805, 82171961, 81801715, 81801716 National Natural Science Foundation of China
- 2018CFB568 National Natural Science Foundation of Hubei
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Affiliation(s)
- Zhenxing Sun
- Anhui Medical University, Hefei, 230031, China
- Department of Ultrasound, The First Affiliated Hospital of Wannan Medical College, Wuhu, 241001, China
- Department of Ultrasound Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Province Key Laboratory of Molecular Imaging, 430022, Wuhan, China
| | - Yu Cai
- Department of Ultrasound Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Province Key Laboratory of Molecular Imaging, 430022, Wuhan, China
| | - Yihan Chen
- Department of Ultrasound Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Province Key Laboratory of Molecular Imaging, 430022, Wuhan, China
| | - Qiaofeng Jin
- Department of Ultrasound Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Province Key Laboratory of Molecular Imaging, 430022, Wuhan, China
| | - Ziming Zhang
- Department of Ultrasound Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Province Key Laboratory of Molecular Imaging, 430022, Wuhan, China
| | - Li Zhang
- Department of Ultrasound Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Province Key Laboratory of Molecular Imaging, 430022, Wuhan, China
| | - Yuman Li
- Department of Ultrasound Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Province Key Laboratory of Molecular Imaging, 430022, Wuhan, China
| | - Lei Huang
- Department of Ultrasound Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Province Key Laboratory of Molecular Imaging, 430022, Wuhan, China
| | - Jing Wang
- Department of Ultrasound Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Province Key Laboratory of Molecular Imaging, 430022, Wuhan, China
| | - Yali Yang
- Department of Ultrasound Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Province Key Laboratory of Molecular Imaging, 430022, Wuhan, China
| | - Qing Lv
- Department of Ultrasound Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Province Key Laboratory of Molecular Imaging, 430022, Wuhan, China
| | - Zhengyang Han
- Department of Ultrasound Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
- Hubei Province Key Laboratory of Molecular Imaging, 430022, Wuhan, China.
- Department of Ultrasound, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
| | - Mingxing Xie
- Department of Ultrasound Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
- Hubei Province Key Laboratory of Molecular Imaging, 430022, Wuhan, China.
| | - Xiangming Zhu
- Anhui Medical University, Hefei, 230031, China.
- Department of Ultrasound, The First Affiliated Hospital of Wannan Medical College, Wuhu, 241001, China.
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13
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Wang W, Tayier B, Guan L, Yan F, Mu Y. Optimization of the cotransfection of SERCA2a and Cx43 genes for myocardial infarction complications. Life Sci 2023; 331:122067. [PMID: 37659592 DOI: 10.1016/j.lfs.2023.122067] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Revised: 08/27/2023] [Accepted: 08/30/2023] [Indexed: 09/04/2023]
Abstract
As our previous study showed, the therapeutic effect of two genes (SERCA2a and Cx43) on heart failure after myocardial infarction (MI) was greater than that of single gene (SERCA2a or Cx43) therapy for bone marrow stem cell (BMSC) transplantation. Based on previous research, the aim of this study was to investigate the optimal ratio of codelivery of SERCA2a and Cx43 genes for MI therapy after biotinylated microbubble (BMB) transplantation via ultrasonic-targeted microbubble destruction (UTMD). Forty rats underwent left anterior descending (LAD) ligation and BMSC injection into the infarct and border zones. Four weeks later, the genes SERCA2a and Cx43 were codelivered at different ratios (1:1, 1:2 and 2:1) into the infarcted heart via UTMD. Cardiac mechanoelectrical function was determined at 4 wks after gene delivery, and the hearts of the rats were harvested for measurement of MI size and detection of SERCA2a and Cx43 expression. Q-PCR analysis of the expression of Nkx2.5 and GATA4 in the myocardial infarct zone and measurement of neovascularization in infarcted hearts. After comparing the therapeutic effects of different cogene ratios, the SERCA2a/Cx43-1:2 group showed remarkable cardiac electrical stability and strengthened the role of anti-arrhythmia. In conclusion, the optimum ratio of the SERCA2a/Cx43 gene is 1:2, which is advantageous for maintaining cardiac electrophysiological stability.
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Affiliation(s)
- Wei Wang
- Department of Echocardiography, Xinjiang Medical University Affiliated First Hospital, Urumqi, China; Xinjiang Key Laboratory of Ultrasound Medicine, Urumqi, China; Department of Ultrasound, Urumqi Friendship Hospital, Urumqi, China
| | - Baihetiya Tayier
- Department of Echocardiography, Xinjiang Medical University Affiliated First Hospital, Urumqi, China; Xinjiang Key Laboratory of Ultrasound Medicine, Urumqi, China
| | - Lina Guan
- Department of Echocardiography, Xinjiang Medical University Affiliated First Hospital, Urumqi, China; Xinjiang Key Laboratory of Ultrasound Medicine, Urumqi, China
| | - Fei Yan
- CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
| | - Yuming Mu
- Department of Echocardiography, Xinjiang Medical University Affiliated First Hospital, Urumqi, China; Xinjiang Key Laboratory of Ultrasound Medicine, Urumqi, China.
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14
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Anjiki K, Matsumoto T, Kuroda Y, Fujita M, Hayashi S, Nakano N, Tsubosaka M, Kamenaga T, Takashima Y, Kikuchi K, Ikuta K, Onoi Y, Tachibana S, Suda Y, Wada K, Matsushita T, Kuroda R. Heterogeneous Cells as well as Adipose-Derived Stromal Cells in Stromal Vascular Fraction Contribute to Enhance Anabolic and Inhibit Catabolic Factors in Osteoarthritis. Stem Cell Rev Rep 2023; 19:2407-2419. [PMID: 37477775 DOI: 10.1007/s12015-023-10589-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/07/2023] [Indexed: 07/22/2023]
Abstract
The stromal-vascular fraction (SVF), comprising heterogeneous cell populations and adipose-derived stromal cells (ADSCs), has therapeutic potential against osteoarthritis (OA); however, the underlying mechanism remains elusive. This study aimed to investigate the therapeutic effects of heterogeneous cells in rabbit SVF on rabbit chondrocytes. Rabbit SVF and ADSCs were autografted into knees at OA onset. The SVF (1 × 105) and low-dose ADSCs (lADSC; 1 × 104) groups adjusted for their stromal cell content were compared. Animals were euthanized 8 and 12 weeks after OA onset for macroscopic and histological analyses of OA progression and synovitis. Immunohistochemical and real-time polymerase chain reaction assessments were conducted. In vitro, immune-fluorescent double staining was performed for SVF to stain macrophages with F4/80, CD86(M1), and CD163(M2). OA progression was markedly suppressed, and synovitis was reduced in the SVF groups (OARSI histological score 8 W: 6.8 ± 0.75 vs. 3.8 ± 0.75, p = 0.001; 12 W: 8.8 ± 0.4 vs. 5.4 ± 0.49, p = 0.0002). The SVF groups had higher expression of collagen II and SOX9 in cartilage and TGF-β and IL-10 in the synovium, lower expression of MMP-13, and lower macrophage M1/M2 ratio than the lADSC groups. Immunofluorescent double staining revealed a markedly higher number of M2 than that of M1 macrophages in the SVF. The therapeutic effects of SVF on chondrocytes were superior than those of lADSCs, with enhanced anabolic and inhibited catabolic factors. Heterogeneous cells, mainly M2 macrophages in the SVF, enhanced growth factor secretion and chondrocyte-protective cytokines, thus benefiting chondrocytes and knee joint homeostasis. Overall, the SVF is a safe, relatively simple, and a useful treatment option for OA.
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Affiliation(s)
- Kensuke Anjiki
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Tomoyuki Matsumoto
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
| | - Yuichi Kuroda
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Masahiro Fujita
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Shinya Hayashi
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Naoki Nakano
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Masanori Tsubosaka
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Tomoyuki Kamenaga
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Yoshinori Takashima
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Kenichi Kikuchi
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Kenmei Ikuta
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Yuma Onoi
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Shotaro Tachibana
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Yoshihito Suda
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Kensuke Wada
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Takehiko Matsushita
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Ryosuke Kuroda
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
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15
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Roohaninasab M, Khodadad F, Sadeghzadeh-Bazargan A, Atefi N, Zare S, Jafarzadeh A, Rahimi ST, Nouri M, Nilforoushzadeh MA, Behrangi E, Goodarzi A. Efficacy of fractional CO 2 laser in combination with stromal vascular fraction (SVF) compared with fractional CO 2 laser alone in the treatment of burn scars: a randomized controlled clinical trial. Stem Cell Res Ther 2023; 14:269. [PMID: 37742019 PMCID: PMC10518108 DOI: 10.1186/s13287-023-03480-8] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2023] [Accepted: 08/29/2023] [Indexed: 09/25/2023] Open
Abstract
BACKGROUND The appearance of skin scars is known as one of the main side effects of skin burns. Stromal vascular fraction (SVF), as a rich source of cell populations with tissue regeneration properties, plays an important role in the healing of skin lesions. Fractional CO2 lasers have occupied a special place in treating skin lesions, particularly skin scars, since their introduction. Our study aimed to compare the combination of SVF and fractional CO2 laser with fractional CO2 laser alone in the treatment of burn scars. METHOD This double-blind clinical trial study was conducted on ten patients with burn scars that were treated three times with a fractional CO2 laser at site of burn lesions, and one of the two areas studied was randomly injected with SVF. Two months after completion of the procedure, patients' scars were assessed using the Vancouver scar scale (VSS), biometric criteria, and physician and patient satisfaction ratings. RESULTS The results confirmed a significant improvement in VSS, cutometry, R7 criteria, complete density sonography, and skin density sonography in the fractional CO2 laser-treated group. The VSS criteria, epidermal thickness sonography, complete density sonography, and skin density sonography in the group treated with the combination of fractional CO2 laser and SVF also showed significant improvement. The VSS criteria and melanin index of Mexameter in the group treated with SVF in combination with fractional CO2 laser were significantly better than the group treated with fractional CO2 laser alone. Also, physician and patient satisfaction in the group treated with SVF injection in combination with fractional CO2 laser was significantly higher than the other group. CONCLUSION The results confirm the efficacy of SVF injection in combination with fractional CO2 laser in the treatment of burn scars and can be considered as a treatment option for better management of these lesions. TRIAL REGISTRATION The study protocol was retrospectively registered at Iranian Registry of Clinical Trials with code: IRCT20210515051307N1, Registration date: 2021-11-14, URL: https://www.irct.ir/trial/56337 .
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Affiliation(s)
- Masoumeh Roohaninasab
- Department of Dermatology, Rasool Akram Medical Complex Clinical Research Development Center (RCRDC), School of Medicine, Iran University of Medical Sciences (IUMS), Tehran, Iran
- Skin and Stem Cell Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Fariba Khodadad
- Department of Dermatology, Rasool Akram Medical Complex Clinical Research Development Center (RCRDC), School of Medicine, Iran University of Medical Sciences (IUMS), Tehran, Iran
- Skin and Stem Cell Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Afsaneh Sadeghzadeh-Bazargan
- Department of Dermatology, Rasool Akram Medical Complex Clinical Research Development Center (RCRDC), School of Medicine, Iran University of Medical Sciences (IUMS), Tehran, Iran
- Skin and Stem Cell Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Najmolsadat Atefi
- Department of Dermatology, Rasool Akram Medical Complex Clinical Research Development Center (RCRDC), School of Medicine, Iran University of Medical Sciences (IUMS), Tehran, Iran
- Skin and Stem Cell Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Sona Zare
- Skin and Stem Cell Research Center, Tehran University of Medical Sciences, Tehran, Iran
- Laser Application in Medical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Stem Cell and Regenerative Medicine Institute, Sharif University of Technology, Tehran, Iran
- Department of Mechanical Engineering, Sharif University of Technology, Tehran, Iran
| | - Alireza Jafarzadeh
- Department of Dermatology, Rasool Akram Medical Complex Clinical Research Development Center (RCRDC), School of Medicine, Iran University of Medical Sciences (IUMS), Tehran, Iran
| | - Seyyedeh Tahereh Rahimi
- Department of Dermatology, Rasool Akram Medical Complex Clinical Research Development Center (RCRDC), School of Medicine, Iran University of Medical Sciences (IUMS), Tehran, Iran
| | - Maryam Nouri
- Skin and Stem Cell Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Ali Nilforoushzadeh
- Skin and Stem Cell Research Center, Tehran University of Medical Sciences, Tehran, Iran.
- Skin Repair Research Center, Jordan Dermatology and Hair Transplantation Center, Tehran, Iran.
| | - Elham Behrangi
- Department of Dermatology, Rasool Akram Medical Complex Clinical Research Development Center (RCRDC), School of Medicine, Iran University of Medical Sciences (IUMS), Tehran, Iran.
- Skin and Stem Cell Research Center, Tehran University of Medical Sciences, Tehran, Iran.
| | - Azadeh Goodarzi
- Department of Dermatology, Rasool Akram Medical Complex Clinical Research Development Center (RCRDC), School of Medicine, Iran University of Medical Sciences (IUMS), Tehran, Iran
- Skin and Stem Cell Research Center, Tehran University of Medical Sciences, Tehran, Iran
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16
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Jovic D, Preradovic L, Kremenovic M, Jovic F, Antonic M, Aleksic Z, Ljubojevic V. Effect of Donor Site Selection for Fat Grafting on the Yield and Viability of the Stromal Vascular Fraction. Aesthet Surg J 2023; 43:NP704-NP712. [PMID: 37289983 DOI: 10.1093/asj/sjad184] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2023] [Revised: 05/25/2023] [Accepted: 05/30/2023] [Indexed: 06/10/2023] Open
Abstract
BACKGROUND The efficacy of stromal vascular fraction (SVF) treatment, or stem cell treatment, directly depends on the SVF cell count and the cells' viability. The SVF cell count and viability are in direct correlation with the adipose tissue harvesting site that yields SVF cells, making this research a contribution to developing tissue guidance. OBJECTIVES The aim of this study was to investigate the importance of harvesting subcutaneous adipose tissue-derived SVF cells on the concentration and viability of SVF. METHODS Adipose tissue was collected by vibration-assisted liposuction from the regions of the upper and lower abdomen, lumbar region, and inner thigh region. With the semiautomatic UNISTATION 2nd Version system, the obtained fat was chemically processed (with collagenase enzyme) and a concentrate of SVF cells was obtained by centrifugation. These samples were then analyzed with the Luna-Stem Counter device to measure the number and viability of SVF cells. RESULTS When comparing the regions of the upper abdomen, lower abdomen, lumbar region, and inner thigh, the highest concentration of SVF was found in the lumbar region, specifically at an average of 97,498.00 per 1.0 mL of concentrate. The lowest concentration was found in the upper abdominal region. When ranking the viability values, the highest cell viability of SVF was observed in the lumbar region, measuring 36.6200%. The lowest viability was found in the upper abdominal region, measuring 24.4967%. CONCLUSIONS By comparing the upper and lower abdominal, lumbar, and inner thigh regions, the authors have come to the conclusion that, on average, the largest number of cells with the highest viability was obtained from the lumbar region.
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Empagliflozin-Pretreated Mesenchymal Stem Cell-Derived Small Extracellular Vesicles Attenuated Heart Injury. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2023; 2023:7747727. [PMID: 36852325 PMCID: PMC9966826 DOI: 10.1155/2023/7747727] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Revised: 01/31/2023] [Accepted: 02/02/2023] [Indexed: 02/20/2023]
Abstract
Objective Small extracellular vesicles derived from mesenchymal stem cells (MSCs) play important roles in cardiac protection. Studies have shown that the cardiovascular protection of sodium-glucose cotransporter 2 inhibitor (SGLT2i) is independent of its hypoglycemic effect. This study is aimed at investigating whether small extracellular vesicles derived from MSCs pretreated with empagliflozin (EMPA) has a stronger cardioprotective function after myocardial infarction (MI) and to explore the underlying mechanisms. Methods and Results We evaluated the effects of EMPA on MSCs and the effects of EMPA-pretreated MSCs-derived small extracellular vesicles (EMPA-sEV) on myocardial apoptosis, angiogenesis, and cardiac function after MI in vitro and in vivo. The small extracellular vesicles of control MSCs (MSC-sEV) and EMPA-pretreated MSCs were extracted, respectively. Small extracellular vesicles were cocultured with apoptotic H9c2 cells induced by H2O2 or injected into the infarcted area of the Sprague-Dawley (SD) rat myocardial infarction model. EMPA increased the cell viability, migration ability, and inhibited apoptosis and senescence of MSCs. In vitro, EMPA-sEV inhibited apoptosis of H9c2 cells compared with the control group (MSC-sEV). In the SD rat model of MI, EMPA-sEV inhibited myocardial apoptosis and promoted angiogenesis in the infarct marginal areas compared with the MSC-sEV. Meanwhile, EMPA-sEV reduced infarct size and improved cardiac function. Through small extracellular vesicles (miRNA) sequencing, we found several differentially expressed miRNAs, among which miR-214-3p was significantly elevated in EMPA-sEV. Coculture of miR-214-3p high expression MSC-derived small extracellular vesicles with H9c2 cells produced similar protective effects. In addition, miR-214-3p was found to promote AKT phosphorylation in H9c2 cells. Conclusions Our data suggest that EMPA-sEV significantly improve cardiac repair after MI by inhibiting myocardial apoptosis. miR-214-3p at least partially mediated the myocardial protection of EMPA-sEV through the AKT signaling pathway.
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Ha JY, Lee EH, Chun SY, Lee JN, Ha YS, Chung JW, Yoon BH, Jeon M, Kim HT, Kwon TG, Yoo ES, Kim BS. The Efficacy and Safety of a Human Perirenal Adipose Tissue-Derived Stromal Vascular Fraction in an Interstitial Cystitis Rat Model. Tissue Eng Regen Med 2023; 20:225-237. [PMID: 36600004 PMCID: PMC10070579 DOI: 10.1007/s13770-022-00505-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2022] [Revised: 09/19/2022] [Accepted: 10/27/2022] [Indexed: 01/06/2023] Open
Abstract
BACKGROUND Interstitial cystitis (IC) is a chronic and intractable disease that can severely deteriorate patients' quality of life. Recently, stem cell therapy has been introduced as a promising alternative treatment for IC in animal models. We aimed to verify the efficacy and safety of the human perirenal adipose tissue-derived stromal vascular fraction (SVF) in an IC rat model. METHODS From eight-week-old female rats, an IC rat model was established by subcutaneous injection of 200 μg of uroplakin3A. The SVF was injected into the bladder submucosal layer of IC rats, and pain scale analysis, awakening cytometry, and histological and gene analyses of the bladder were performed. For the in vivo safety analysis, genomic DNA purification and histological analysis were also performed to check tumorigenicity and thrombus formation. RESULTS The mean pain scores in the SVF 20 μl group were significantly lower on days 7 and 14 than those in the control group, and bladder intercontraction intervals were significantly improved in the SVF groups in a dose-dependent manner. Regeneration of the bladder epithelium, basement membrane, and lamina propria was observed in the SVF group. In the SVF groups, however, bladder fibrosis and the expression of inflammatory markers were not significantly improved compared to those in the control group. CONCLUSION This study demonstrated that a perirenal adipose tissue-derived SVF is a promising alternative for the management of IC in terms of improving bladder pain and overactivity.
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Affiliation(s)
- Ji Yong Ha
- Department of Urology, Dongsan Medical Center, Keimyung University School of Medicine, Daegu, Republic of Korea
| | - Eun Hye Lee
- Joint Institute for Regenerative Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - So Young Chun
- BioMedical Research Institute, Kyungpook National University Hospital, Daegu, Republic of Korea
| | - Jun Nyung Lee
- Department of Urology, School of Medicine, Kyungpook National University, Chilgok Kyungpook National University Hospital, Daegu, Republic of Korea
| | - Yun-Sok Ha
- Department of Urology, School of Medicine, Kyungpook National University, Chilgok Kyungpook National University Hospital, Daegu, Republic of Korea
| | - Jae-Wook Chung
- Department of Urology, School of Medicine, Kyungpook National University, Chilgok Kyungpook National University Hospital, Daegu, Republic of Korea
| | - Bo Hyun Yoon
- Joint Institute for Regenerative Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Minji Jeon
- Joint Institute for Regenerative Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Hyun Tae Kim
- Department of Urology, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, 41944, Republic of Korea
| | - Tae Gyun Kwon
- Department of Urology, School of Medicine, Kyungpook National University, Chilgok Kyungpook National University Hospital, Daegu, Republic of Korea
| | - Eun Sang Yoo
- Department of Urology, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, 41944, Republic of Korea.
| | - Bum Soo Kim
- Department of Urology, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, 41944, Republic of Korea.
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Fujita M, Matsumoto T, Sobajima S, Tsubosaka M, Matsushita T, Iwaguro H, Kuroda R. Clinical and Radiological Comparison of Single and Double Intra-articular Injection of Adipose-Derived Stromal Vascular Fraction for Knee Osteoarthritis. Cell Transplant 2023; 32:9636897231190175. [PMID: 37551027 PMCID: PMC10411282 DOI: 10.1177/09636897231190175] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Revised: 06/27/2023] [Accepted: 07/11/2023] [Indexed: 08/09/2023] Open
Abstract
The aim of the article is to compare the clinical and radiological outcomes between single and double stromal vascular fraction (SVF) cell injections in patients with knee osteoarthritis (OA). We included 54 patients treated for varus knee OA with intra-articular SVF cell injection. They were divided into two groups: those who received one injection and those who received two. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, knee range of motion, and knee muscle force were assessed at baseline and 3, 6, 12, and 24 months after the first injection. The preoperative hip-knee-ankle (HKA) angle was evaluated using plain radiographs, and T2 mapping values were assessed. The total WOMAC score improved significantly in the single injection group from 3 to 24 months, but the total WOMAC score in the double injection group improved significantly at 24 months. The T2 mapping values in both the groups improved, with a significant difference at 12 months. The preoperative mean HKA angle and the correlation coefficients between the HKA angle and the total WOMAC score and between the HKA angle and the T2 mapping value of the medial femur were significant. In conclusion, double injections may provide more satisfactory treatment outcomes in patients with severe varus knee alignment. This clinical trial is registered in the Japanese Ministry of Health, Labour and Welfare (URL: https://saiseiiryo.mhlw.go.jp/published_plan/index/2) with the registration name "Cell transplantation therapy for osteoarthritis using autologous subcutaneous adipose tissue-derived regenerative (stem) cells (ADRCs)," and the registration number was "PB5160012."
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Affiliation(s)
- Masahiro Fujita
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Tomoyuki Matsumoto
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Satoshi Sobajima
- Department of Orthopaedic Surgery, Sobajima Clinic, Higashiosaka, Japan
| | - Masanori Tsubosaka
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Takehiko Matsushita
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Hideki Iwaguro
- Department of Orthopaedic Surgery, Sobajima Clinic, Higashiosaka, Japan
| | - Ryosuke Kuroda
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
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20
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Chen W, He Z, Li S, Wu Z, Tan J, Yang W, Li G, Pan X, Liu Y, Lyu FJ, Li W. The Effect of Tissue Stromal Vascular Fraction as Compared to Cellular Stromal Vascular Fraction to Treat Anal Sphincter Incontinence. BIOENGINEERING (BASEL, SWITZERLAND) 2022; 10:bioengineering10010032. [PMID: 36671604 PMCID: PMC9854502 DOI: 10.3390/bioengineering10010032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Revised: 11/30/2022] [Accepted: 12/12/2022] [Indexed: 12/28/2022]
Abstract
BACKGROUND The long-term prognosis of current treatments for anal sphincter incontinence (ASI) is poor. Here, we explored the efficacy of tissue adipose stromal vascular fraction SVF (tSVF) on ASI and compared it to that of cellular SVF (cSVF). We then investigated possible mechanisms. METHODS Rat cSVF and tSVF were isolated and labeled with DIL. One day after modeling, three groups received phosphate-buffered saline (PBS), cSVF, tSVF, respectively. The control group received nil modeling nor any treatments. The effect was assessed by function test for anal pressure and electromyography, and staining for fiber content, proliferation and differentiation at day 5 and day 10. RESULTS cSVF injection resulted in faster healing than tSVF. The cSVF group showed significant improvement on anal pressure on day 10. For the electromyography test, cSVF showed significant improvement for the frequencies on day 10, and for the peak values on both time points, while tSVF showed significant improvement for the peak values on day 10. The two SVF both alleviated fibrosis. Immunofluorescence tracing identified differentiation of some injected cells towards myosatellite cells and smooth muscle cells in both SVF groups. For all the tests, the tSVF group tends to have similar or lower effects than the cSVF group with no significant difference. CONCLUSION cSVF and tSVF are both safe and effective in treating ASI, while the effect of cSVF is slighter higher than tSVF.
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Affiliation(s)
- Wenbin Chen
- Department of Colorectal and Anal Surgery, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou 510641, China
| | - Zijian He
- Department of Colorectal and Anal Surgery, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou 510641, China
| | - Shuyu Li
- School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510641, China
| | - Zixin Wu
- Department of Colorectal and Anal Surgery, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou 510641, China
| | - Jin Tan
- The Sixth Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou 510641, China
| | - Weifeng Yang
- Department of Colorectal and Anal Surgery, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou 510641, China
| | - Guanwei Li
- Department of Colorectal and Anal Surgery, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou 510641, China
| | - Xiaoling Pan
- The Sixth Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou 510641, China
| | - Yuying Liu
- The Sixth Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou 510641, China
| | - Feng-Juan Lyu
- The Sixth Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou 510641, China
- Correspondence: (F.-J.L.); (W.L.)
| | - Wanglin Li
- Department of Colorectal and Anal Surgery, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou 510641, China
- Correspondence: (F.-J.L.); (W.L.)
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Maene A, Deniz G, Bouland C, Lagneaux L, Philippart P, Buxant F. Suburethral implantation of autologous regenerative cells for female stress urinary incontinence management: Results of a pilot study. Eur J Obstet Gynecol Reprod Biol 2022; 278:38-44. [PMID: 36113285 DOI: 10.1016/j.ejogrb.2022.08.028] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2022] [Revised: 08/23/2022] [Accepted: 08/30/2022] [Indexed: 11/29/2022]
Abstract
OBJECTIVES To assess the feasibility and the safety of treating female stress urinary incontinence (SUI) with suburethral implantation of a mixture of the stromal vascular fraction from adipose tissue and leukocyte-and platelet-rich-fibrin. METHODS Patients with SUI were treated with a mixture of stromal vascular fraction and leukocyte-and platelet-rich fibrin. The stromal vascular fraction was obtained from enzymatic digestion of autologous adipose-tissue and added to an leukocyte-and platelet-rich-fibrin membrane. The mixture was transvaginally implanted into the suburethral area. A fraction of the Stromal vascular fraction sample was used for cellular characterization. Patients were followed for 9 months. Every 3 months, the patients were clinically evaluated with a cough- stress test and a validated-questionnaire. An MRI was performed preoperatively and 3 months after the procedure to assess tissue changes. RESULTS Ten patients received the surgical procedure. The validated-questionnaire revealed a subjective SUI improvement in nine patients 3 months after the operation and in seven patients 9 months after the operation. Eight, six, and four patients achieved a negative cough-stress test 3, 6 and 9 months post-injection, respectively. Flow cytometric analysis of stromal vascular fraction cell phenotypes revealed predominantly mesenchymal and endothelial cell heterogeneity. In total, we injected 0,18 × 106 to 13,6 × 106 cells. No adverse events were observed peri- or postoperatively. CONCLUSION These preliminary results suggest that the suburethral implantation of a combination of SVF and l-PRF is a feasible and safe modality for treating female SUI. However, evidence is lacking and further research are needed to clarify the respective roles of SVF and l-PRF in female SUI treatment.
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Affiliation(s)
- Anne Maene
- Université Libre de Bruxelles, Medicine Faculty, route de Lennik 808, 1070 Brussels, Belgium.
| | - Gulcan Deniz
- Departments of Gynecology and Obstetrics, IRIS South Hospital, rue Jean-Paquot 63, 1050 Brussels, Belgium
| | - Cyril Bouland
- Université Libre de Bruxelles, Medicine Faculty, route de Lennik 808, 1070 Brussels, Belgium; Departement of Stomatology and maxillofacial Surgery, CHU Saint-Pierre, 322 Rue Haute, 1000 Brussels, Belgium; Laboratory of Clinical Cell Therapy, Jules Bordet Institute, Université Libre de Bruxelles, campus Erasme, Route de Lennik 808, 1070 Brussels, Belgium
| | - Laurence Lagneaux
- Laboratory of Clinical Cell Therapy, Jules Bordet Institute, Université Libre de Bruxelles, campus Erasme, Route de Lennik 808, 1070 Brussels, Belgium
| | - Pierre Philippart
- Université Libre de Bruxelles, Medicine Faculty, route de Lennik 808, 1070 Brussels, Belgium; Departement of Stomatology and maxillofacial Surgery, IRIS south Hospital, rue Docteur Huet, 1070 Brussels, Belgium
| | - Fréderic Buxant
- Departments of Gynecology and Obstetrics, IRIS South Hospital, rue Jean-Paquot 63, 1050 Brussels, Belgium
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Lana JFSD, Lana AVSD, da Fonseca LF, Coelho MA, Marques GG, Mosaner T, Ribeiro LL, Azzini GOM, Santos GS, Fonseca E, de Andrade MAP. Stromal Vascular Fraction for Knee Osteoarthritis - An Update. J Stem Cells Regen Med 2022; 18:11-20. [PMID: 36003656 DOI: 10.46582/jsrm.1801003] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2021] [Accepted: 12/10/2021] [Indexed: 11/19/2022]
Abstract
Orthobiologics never cease to cause popularity within the medical science field, distinctly in regenerative medicine. Recently, adipose tissue has been an object of interest for many researchers and medical experts due to the fact that it represents a novel and potential cell source for tissue engineering and regenerative medicine purposes. Stromal vascular fraction (SVF), for instance, which is an adipose tissue-derivative, has generated optimistic results in many scenarios. Its biological potential can be harnessed and administered into injured tissues, particularly areas in which standard healing is disrupted. This is a typical feature of osteoarthritis (OA), a common degenerative joint disease which is outlined by persistent inflammation and destruction of surrounding tissues. SVF is known to carry a large amount of stem and progenitor cells, which are able to perform self-renewal, differentiation, and proliferation. Furthermore, they also secrete several cytokines and several growth factors, effectively sustaining immune modulatory effects and halting the escalated pro-inflammatory status of OA. Although SVF has shown interesting results throughout the medical community, additional research is still highly desirable in order to further elucidate its potential regarding musculoskeletal disorders, especially OA.
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Affiliation(s)
| | | | - Lucas Furtado da Fonseca
- Orthopaedic Department - Universidade Federal de São Paulo - Escola Paulista de Medicina, São Paulo - SP, Brazil
| | - Marcelo Amaral Coelho
- IOC - Instituto do Osso e da Cartilagem / The Bone and Cartilage Institute, Indaiatuba - SP, Brazil
| | | | - Tomas Mosaner
- IOC - Instituto do Osso e da Cartilagem / The Bone and Cartilage Institute, Indaiatuba - SP, Brazil
| | | | | | - Gabriel Silva Santos
- IOC - Instituto do Osso e da Cartilagem / The Bone and Cartilage Institute, Indaiatuba - SP, Brazil
| | - Eduardo Fonseca
- IOC - Instituto do Osso e da Cartilagem / The Bone and Cartilage Institute, Indaiatuba - SP, Brazil
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23
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Fujita M, Matsumoto T, Hayashi S, Hashimoto S, Nakano N, Maeda T, Kuroda Y, Takashima Y, Kikuchi K, Anjiki K, Ikuta K, Onoi Y, Tachibana S, Matsushita T, Iwaguro H, Sobajima S, Hiranaka T, Kuroda R. Paracrine effect of the stromal vascular fraction containing M2 macrophages on human chondrocytes through the Smad2/3 signaling pathway. J Cell Physiol 2022; 237:3627-3639. [PMID: 35766589 DOI: 10.1002/jcp.30823] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2021] [Revised: 05/27/2022] [Accepted: 06/17/2022] [Indexed: 11/08/2022]
Abstract
The adipose-derived stromal vascular fraction (SVF) is composed of a heterogeneous mix of adipose-derived stem cells (ADSCs), macrophages, pericytes, fibroblasts, blood, and other cells. Previous studies have found that the paracrine effects of SVF cells may be therapeutic, but their role in osteoarthritis treatment remains unclear. This study aimed to investigate the therapeutic effect of SVF cells on chondrocytes. Chondrocytes were seeded on culture plates alone (control) or cocultured with SVF or ADSCs on cell culture inserts. After 48 h of coculture, chondrocyte collagen II, tissue inhibitors of metalloproteinases-3 (TIMP-3), and matrix metalloproteinases-13 (MMP-13) messenger RNA (mRNA) expression levels were evaluated using reverse-transcription polymerase chain reaction, and the transforming growth factor-β (TGF-β) levels in the supernatant were measured using ELISA. Immunohistochemical staining and flow cytometry were used to evaluate the macrophages in the SVF. These macrophages were characterized according to phenotype using the F4/80, CD86, and CD163 markers. To determine whether the Smad2/3 signaling pathways were involved, the chondrocytes were pre-treated with a Smad2/3 phosphorylation inhibitor and stimulated with the SVF, and then Smad2/3 phosphorylation levels were analyzed using western blot. The mRNA expression levels of various paracrine factors and chondrocyte pellet size were also assessed. Collagen II and TIMP-3 expression were higher in the SVF group than in the ADSC group and controls, while MMP-13 expression was the highest in the ADSC group and the lowest in the controls. TGF-β levels in the SVF group were also elevated. Immunohistochemical staining and flow cytometry revealed that the macrophages in the SVF were of the anti-inflammatory phenotype. Western blot analysis showed that the SVF increased Smad2/3 phosphorylation, while Smad2/3 inhibitors decreased phosphorylation. Smad2/3 inhibitors also reduced the expression of various other paracrine factors and decreased chondrocyte pellet size. These findings suggested that the paracrine effect of heterogeneous cells, such as anti-inflammatory macrophages, in the SVF partly supports chondrocyte regeneration through TGF-β-induced Smad2/3 phosphorylation.
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Affiliation(s)
- Masahiro Fujita
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Tomoyuki Matsumoto
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Shinya Hayashi
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Shingo Hashimoto
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Naoki Nakano
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Toshihisa Maeda
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Yuichi Kuroda
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Yoshinori Takashima
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Kenichi Kikuchi
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Kensuke Anjiki
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Kemmei Ikuta
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Yuma Onoi
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Shotaro Tachibana
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Takehiko Matsushita
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Hideki Iwaguro
- Department of Orthopaedic Surgery, Sobajima Clinic, Osaka, Japan
| | - Satoshi Sobajima
- Department of Orthopaedic Surgery, Sobajima Clinic, Osaka, Japan
| | - Takafumi Hiranaka
- Department of Orthopaedic Surgery and Joint Surgery Centre, Takatsuki General Hospital, Osaka, Japan
| | - Ryosuke Kuroda
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
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24
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Dai LG, Huang NC, Kang LY, Fu KY, Hsieh PS, Dai NT. An In Vitro Study of the Effects of Mechanical and Enzymatic Isolation of Stromal Vascular Fraction on Wound Healing. Ann Plast Surg 2022; 88:S13-S21. [PMID: 35225844 DOI: 10.1097/sap.0000000000003087] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
ABSTRACT The adipose-derived stromal vascular fraction (SVF) is considered to be an attractive source of stem cells in cell therapy. Besides stem cells, it also contains functional cells, such as macrophages, precursor cells, somatic stem cells, and pericytes. Collagenase digestion is the most frequently used method to isolate SVF, but it is time-consuming and costly and has some problems, such as infectious agents and immune reactions. In this research, we compared the yield, cell population ratios, and cell viability when isolating SVF by the ultrasonic physics (U-SVF) method and traditional enzymatic method (E-SVF). Then, we isolated exosomes from U-SVF and E-SVF, respectively, and cocultured them with fibroblasts to investigate the potential of applying this cell secretion in wound repair. The results showed that there was no significant difference between the ultrasonic method and enzymatic method in terms of cell viability, cell numbers, or the expression of CD markers of stem cells. However, exosome analysis identified a greater number and smaller size of exosome particles obtained by U-SVF. In terms of cell proliferation efficiency, although the proliferation efficiency of U-SVF was lower than that of E-SVF. Trilineage differentiation experiments revealed that both E-SVF and U-SVF had good differentiation ability, owing to high stem cell content. Finally, E-SVF and U-SVF exosomes were cocultured with fibroblasts. The efficiency of fibroblast migration increased in the SVF exosome treated groups, and the expression of related genes (integrin α5β1) was slightly upregulated; however, the expression of FAK, AKT, ERK, and RhoA was significantly upregulated at 24 hours. From the abovementioned experiments, we found that there was no significant difference in stem cell-related characteristics between SVF isolated by ultrasonic cavitation and SVF isolated by the enzymatic method. In addition, exosomes secreted by SVF may have excellent therapeutic effect on skin injuries, which provides a new viewpoint and therapeutic strategy for soft tissue repair.
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Affiliation(s)
- Lien-Guo Dai
- From the Department of Orthopaedic Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei
| | - Nien-Chi Huang
- Division of Plastic and Reconstructive Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China
| | - Lan-Ya Kang
- Division of Plastic and Reconstructive Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China
| | - Keng-Yen Fu
- Division of Plastic and Reconstructive Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China
| | - Pai-Shan Hsieh
- Division of Plastic and Reconstructive Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China
| | - Niann-Tzyy Dai
- Division of Plastic and Reconstructive Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China
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25
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El-Kadiry AEH, Rafei M, Shammaa R. Cell Therapy: Types, Regulation, and Clinical Benefits. Front Med (Lausanne) 2021; 8:756029. [PMID: 34881261 PMCID: PMC8645794 DOI: 10.3389/fmed.2021.756029] [Citation(s) in RCA: 99] [Impact Index Per Article: 24.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Accepted: 11/01/2021] [Indexed: 12/12/2022] Open
Abstract
Cell therapy practices date back to the 19th century and continue to expand on investigational and investment grounds. Cell therapy includes stem cell- and non-stem cell-based, unicellular and multicellular therapies, with different immunophenotypic profiles, isolation techniques, mechanisms of action, and regulatory levels. Following the steps of their predecessor cell therapies that have become established or commercialized, investigational and premarket approval-exempt cell therapies continue to provide patients with promising therapeutic benefits in different disease areas. In this review article, we delineate the vast types of cell therapy, including stem cell-based and non-stem cell-based cell therapies, and create the first-in-literature compilation of the different "multicellular" therapies used in clinical settings. Besides providing the nuts and bolts of FDA policies regulating their use, we discuss the benefits of cell therapies reported in 3 therapeutic areas-regenerative medicine, immune diseases, and cancer. Finally, we contemplate the recent attention shift toward combined therapy approaches, highlighting the factors that render multicellular therapies a more attractive option than their unicellular counterparts.
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Affiliation(s)
- Abed El-Hakim El-Kadiry
- Laboratory of Thrombosis and Hemostasis, Montreal Heart Institute, Research Center, Montreal, QC, Canada
- Department of Biomedical Sciences, Université de Montréal, Montreal, QC, Canada
| | - Moutih Rafei
- Department of Pharmacology and Physiology, Université de Montréal, Montreal, QC, Canada
- Department of Microbiology, Infectious Diseases and Immunology, Université de Montréal, Montreal, QC, Canada
- Molecular Biology Program, Université de Montréal, Montreal, QC, Canada
- Department of Microbiology and Immunology, McGill University, Montreal, QC, Canada
| | - Riam Shammaa
- Canadian Centre for Regenerative Therapy, Toronto, ON, Canada
- Department of Family and Community Medicine, University of Toronto, Toronto, ON, Canada
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26
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Sharma S, Muthu S, Jeyaraman M, Ranjan R, Jha SK. Translational products of adipose tissue-derived mesenchymal stem cells: Bench to bedside applications. World J Stem Cells 2021; 13:1360-1381. [PMID: 34786149 PMCID: PMC8567449 DOI: 10.4252/wjsc.v13.i10.1360] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 07/02/2021] [Accepted: 08/30/2021] [Indexed: 02/06/2023] Open
Abstract
With developments in the field of tissue engineering and regenerative medicine, the use of biological products for the treatment of various disorders has come into the limelight among researchers and clinicians. Among all the available biological tissues, research and exploration of adipose tissue have become more robust. Adipose tissue engineering aims to develop by-products and their substitutes for their regenerative and immunomodulatory potential. The use of biodegradable scaffolds along with adipose tissue products has a major role in cellular growth, proliferation, and differentiation. Adipose tissue, apart from being the powerhouse of energy storage, also functions as the largest endocrine organ, with the release of various adipokines. The progenitor cells among the heterogeneous population in the adipose tissue are of paramount importance as they determine the capacity of regeneration of these tissues. The results of adipose-derived stem-cell assisted fat grafting to provide numerous growth factors and adipokines that improve vasculogenesis, fat graft integration, and survival within the recipient tissue and promote the regeneration of tissue are promising. Adipose tissue gives rise to various by-products upon processing. This article highlights the significance and the usage of various adipose tissue by-products, their individual characteristics, and their clinical applications.
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Affiliation(s)
- Shilpa Sharma
- Department of Pediatric Surgery, All India Institute of Medical Sciences, New Delhi 110029, India
- Indian Stem Cell Study Group, Lucknow, Uttar Pradesh 226010, India
| | - Sathish Muthu
- Indian Stem Cell Study Group, Lucknow, Uttar Pradesh 226010, India
- Department of Orthopaedics, Government Medical College and Hospital, Dindigul, Tamil Nadu 624304, India
- Research Scholar, Department of Biotechnology, School of Engineering and Technology, Greater Noida, Sharda University, Uttar Pradesh 201306, India
| | - Madhan Jeyaraman
- Indian Stem Cell Study Group, Lucknow, Uttar Pradesh 226010, India
- Research Scholar, Department of Biotechnology, School of Engineering and Technology, Greater Noida, Sharda University, Uttar Pradesh 201306, India
- Department of Orthopaedics, School of Medical Sciences and Research, Sharda University, Greater Noida, Uttar Pradesh 201306, India
| | - Rajni Ranjan
- Department of Orthopaedics, School of Medical Sciences and Research, Sharda University, Greater Noida, Uttar Pradesh 201306, India
| | - Saurabh Kumar Jha
- Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida, Uttar Pradesh 201306, India
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27
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Kishta MS, Ahmed HH, Ali MAM, Aglan HA, Mohamed MR. Mesenchymal stem cells seeded onto nanofiber scaffold for myocardial regeneration. Biotech Histochem 2021; 97:322-333. [PMID: 34607472 DOI: 10.1080/10520295.2021.1979251] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022] Open
Abstract
Cardiac disease is the leading cause of mortality and disability worldwide. We investigated the role of undifferentiated adipose tissue-derived mesenchymal stem cells (ADMSC) alone and ADMSC seeded onto the electro-spun nanofibers (NF) for reconstructing damaged cardiac tissue in isoprenaline-induced myocardial infarction (MI) in rats. ADMSC were sorted by morphological appearance and by detection of cluster of differentiation (CD) surface antigens. The therapeutic potential of ADMSC for treating MI was evaluated by electrocardiogram (ECG), biochemical analysis, molecular genetic analysis and histological examination. Treatment of MI-challenged rats with ADMSC improved ECG findings, which were corroborated by significant decreases in serum lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) enzyme activities together with reduced serum troponin T (cTnT) and connexin 43 (Cx43) levels. MI model rats treated with ADMSC exhibited a significant increase in serum alpha sarcomeric actin (Actn) and GATA binding protein 4 (GATA4), and NK2 homeobox 5 (NKX2.5) gene expression was decreased following treatment with ADMSC. ADMSC also ameliorated damage to cardiac tissue. The effects of ADMSC seeded onto NF were superior to those of ADMSC alone. ADMSC may be useful for mitigation of MI.
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Affiliation(s)
- Mohamed S Kishta
- Hormones Department, Medical Research Division, National Research Centre, Giza, Egypt.,Stem Cell Lab, Center of Excellence for Advanced Sciences, National Research Centre, Giza, Egypt
| | - Hanaa H Ahmed
- Hormones Department, Medical Research Division, National Research Centre, Giza, Egypt.,Stem Cell Lab, Center of Excellence for Advanced Sciences, National Research Centre, Giza, Egypt
| | - Mohamed A M Ali
- Biochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt
| | - Hadeer A Aglan
- Hormones Department, Medical Research Division, National Research Centre, Giza, Egypt.,Stem Cell Lab, Center of Excellence for Advanced Sciences, National Research Centre, Giza, Egypt
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28
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Tanios E, Ahmed TM, Shafik EA, Sherif MF, Sayed D, Gaber N, Hassan Y. Efficacy of adipose-derived stromal vascular fraction cells in the management of chronic ulcers: a randomized clinical trial. Regen Med 2021; 16:975-988. [PMID: 34596433 DOI: 10.2217/rme-2020-0207] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Background: Cell therapy is a promising method for improving healing in chronic ulcers through delivery of isolated adipose-derived stromal vascular fraction. Objectives: This study investigates the autologous stem cell yield of adipose tissue and its efficacy in chronic ulcers compared with conventional methods. Methods: This study was a randomized controlled trial. After the study design and protocol were established and ethical committee approval was obtained, we enrolled 100 patients divided into study and control groups. In the study group, we performed debridement and autologous stem cell injection every 3 weeks. The control group was treated with debridement and conventional dressing. Assessments included clinical and histological parameters. Results: The study group showed improved healing. Conclusion: Using autologous adipose-derived stromal vascular fraction cells is an effective treatment method for chronic ulcers. This study was registered on the Pan-African Clinical Trial Registry and the number of the registry was PACTR201709002519185.
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Affiliation(s)
- Emil Tanios
- Plastic Surgery Department, Faculty of Medicine, Assiut University, 71111, Egypt
| | - Tohamy M Ahmed
- Plastic Surgery Department, Faculty of Medicine, Assiut University, 71111, Egypt
| | - Engy A Shafik
- Clinical Pathology Department, South Egypt Cancer Institute, Assiut University, 71111, Egypt
| | | | - Douaa Sayed
- Clinical Pathology Department, South Egypt Cancer Institute, Assiut University, 71111, Egypt
| | - Noha Gaber
- Clinical Pathology Department, South Egypt Cancer Institute, Assiut University, 71111, Egypt
| | - Youssef Hassan
- Plastic Surgery Department, Faculty of Medicine, Assiut University, 71111, Egypt
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29
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Use of Autologous Adipose-Derived Stromal Vascular Fractions in Revision Rhinoplasty for Severe Contractures in Asian Patients. Plast Reconstr Surg 2021; 147:401e-411e. [PMID: 33620926 DOI: 10.1097/prs.0000000000007623] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND Autologous adipose-derived stromal vascular fraction treatments have been shown to elicit antiinflammatory, antifibrotic, immunomodulatory, angiogenic, and regenerative effects. Injections of adipose-derived stromal vascular fraction have been used to treat severely scarred tissues. METHODS Revision septorhinoplasty was performed in 40 patients with severely contracted noses. Clinical outcomes and adverse events were compared between one group of patients treated with adjuvant adipose-derived stromal vascular fraction injections and a control group of patients treated with adjuvant 0.9% preservative-free saline injections. RESULTS In the adipose-derived stromal vascular fraction group, nasal lengths were estimated at 4.2 ± 0.2 cm at baseline to 5.1 ± 0.2 cm at 18 months after revision septorhinoplasty. The lengths of nasal tip projection improved from 2.2 ± 0.2 cm at baseline to 2.9 ± 0.1 cm 18 months after surgery. In addition, nasofrontal angles improved from 125.6 ± 5.1 degrees at baseline to 128.1 ± 4.8 degrees 18 months after surgery. Nasolabial angles in the adipose-derived stromal vascular fraction group were estimated at 105.8 ± 6.5 degrees at baseline and 94.9 ± 5.6 degrees 18 months after surgery. Of these, nasal length, nasal tip projection, and nasolabial angle, but not nasofrontal angle, values improved more in the adipose-derived stromal vascular fraction group than in the control group. CONCLUSION Preoperative and postoperative adjuvant adipose-derived stromal vascular fraction treatment markedly improved the therapeutic outcomes of revision rhinoseptoplasty of severely contracted noses without major side effects. CLINICAL QUESTION/LEVEL OF EVIDENCE Therapeutic, III.
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30
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Cannula Size Effect on Stromal Vascular Fraction Content of Fat Grafts. PLASTIC AND RECONSTRUCTIVE SURGERY-GLOBAL OPEN 2021; 9:e3471. [PMID: 33907655 PMCID: PMC8062151 DOI: 10.1097/gox.0000000000003471] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2020] [Accepted: 01/07/2021] [Indexed: 12/13/2022]
Abstract
Background Fat is an active and dynamic tissue composed of adipocytes supported by a structural framework known as the stromal vascular fraction (SVF). SVF is traditionally isolated by enzymatic processing, but new methods are being investigated to isolate it mechanically. Recent studies propose that fat harvested with larger cannulas has a higher survival rate, most likely due to a higher concentration of SVF. Methods Lipoaspirates were obtained from 10 patients who underwent elective liposuction using a 5-mm and a 1-mm cannula attached to a syringe using standard pressure. The fat was aspirated from the same area at adjacent sites. An estimated 5-mm fat particles were also cut down to 1-mm using a micronizer (Marina Medical). A 5-cm3 volume of each sample was compressed through a 0.5-mm opening strainer and rinsed with normal saline to extrude the oil. The resultant SVF left on the strainer was then measured in a 1-cm3 syringe. Results The volume extracted from a 5-mm cannula (mean, 0.23 cm3; SD, 0.10) versus a 1-mm cannula (mean, 0.11 cm3; SD, 0.06) was statistically significant (P = 0.009). An H&E-stained slide from the SVF was obtained for confirmation. Finally, 5-mm fat particles cut down to 1-mm particles using the micronizer resulted in an average volume of 0.20 cm3, which was higher than the average volume harvested with a 1-mm cannula. Conclusions Harvesting with a 5-mm cannula resulted in significantly more SVF than harvesting with a 1-mm cannula. Resizing fat particles harvested with a larger cannula down to 1-mm resulted in higher SVF than SVF obtained with a 1-mm cannula directly.
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31
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Multiple Intravenous Injections of Valproic Acid-Induced Mesenchymal Stem Cell from Human-Induced Pluripotent Stem Cells Improved Cardiac Function in an Acute Myocardial Infarction Rat Model. BIOMED RESEARCH INTERNATIONAL 2020; 2020:2863501. [PMID: 33381545 PMCID: PMC7759411 DOI: 10.1155/2020/2863501] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/21/2020] [Revised: 11/10/2020] [Accepted: 12/02/2020] [Indexed: 11/22/2022]
Abstract
Mounting evidence indicates that the mesenchymal stem cell (MSC) injection is safe and efficacious for treating cardiomyopathy; however, there is limited information relating to multiple intravenous injections of human-induced pluripotent stem cell-derived mesenchymal stem cell (hiPSC-MSC) and long-term evaluation of the cardiac function. In the current study, MSC-like cells were derived from human-induced pluripotent stem cells through valproic acid (VPA) induction and continuous cell passages. The derived spindle-like cells expressed MSC-related markers, secreted angiogenic and immune-regulatory factors, and could be induced to experience chondrogenic and adipogenic differentiation. During the induction process, expression of epithelial-to-mesenchymal transition- (EMT-) related gene N-cadherin and vimentin was upregulated to a very high level, and the expression of pluripotency-related genes Sox2 and Oct4 was downregulated or remained unchanged, indicating that VPA initiated EMT by upregulating the expression of EMT promoting genes and downregulating that of pluripotency-related genes. Two and four intravenous hiPSC-MSC injections (106 cells/per injections) were provided, respectively, to model rats one week after acute myocardial infarction (AMI). Cardiac function parameters were dynamically monitored during a 12-week period. Two and four cell injections significantly the improved left ventricular ejection fraction and left ventricular fractional shortening; four-injection markedly stimulated angiogenesis reduced the scar size and cell apoptosis number in the scar area in comparison with that of the untreated control model rats. Although the difference was insignificant, the hiPSC-MSC administration delayed the increase of left ventricular end-diastolic dimension to different extents compared with that of the PBS-injection control. No perceptible immune reaction symptom or hiPSC-MSC-induced tumour formation was found over 12 weeks. Compared with the PBS-injection control, four injections produced better outcome than two injections; as a result, at least four rounds of MSC injections were suggested for AMI treatment.
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32
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Sun Z, Xie Y, Lee RJ, Chen Y, Jin Q, Lv Q, Wang J, Yang Y, Li Y, Cai Y, Wang R, Han Z, Zhang L, Xie M. Myocardium-targeted transplantation of PHD2 shRNA-modified bone mesenchymal stem cells through ultrasound-targeted microbubble destruction protects the heart from acute myocardial infarction. Theranostics 2020; 10:4967-4982. [PMID: 32308762 PMCID: PMC7163444 DOI: 10.7150/thno.43233] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2019] [Accepted: 03/22/2020] [Indexed: 01/09/2023] Open
Abstract
Ultrasound-targeted microbubble destruction (UTMD) is a promising approach to facilitate the precise delivery of bone marrow stem cells (BMSCs) to the ischemic myocardium. However, stem cell therapy for ischemic myocardium is challenging due to the poor survival of transplanted stem cells under severe ischemic conditions. In this study, we investigated whether myocardium-targeted transplantation of prolyl hydroxylase domain protein 2 (PHD2) shRNA-modified BMSCs by UTMD increases the viability of grafted cells, and enhances their cardioprotective effects in acute myocardial infarction. Methods: BMSCs were transduced with lentiviral PHD2 shRNA, and a novel microbubble formulation was prepared by a thin-film hydration method. In rats, BMSCs with or without PHD2 shRNA modification were transplanted by UTMD after inducing acute myocardium infarction. Effects of PHD2 shRNA on BMSC survival, myocardial apoptosis, angiogenesis, and cardiac function were evaluated. In vitro, anti-apoptotic effects and its mechanisms of PHD2 silencing on BMSC and BMSC-conditioned medium on H9C2 cell were detected. Results: PHD2 shRNA-modified BMSC transplantation by UTMD resulted in increased BMSC survival, reduced myocardial apoptosis, reduced infarct size, increased vascular density, and improved cardiac function compared to the control vector-modified BMSC transplantation by UTMD. PHD2 silencing increased BMSC survival through a HIF-1α-dependent mechanism. The decrease in cardiomyocyte apoptosis by conditioned medium from PHD2 shRNA-treated BMSCs was due to an increase in the expression of insulin-like growth factor (IGF)-1. Conclusions: The delivery of PHD2 shRNA-modified BMSCs by UTMD promoted grafted cell homing and activity, and increased myocardial angiogenesis in the infarcted heart, leading to improved cardiac function. This combination may provide a promising strategy for enhancing the effectiveness of stem cell therapy after acute myocardial infarction.
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33
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Yin S, Yang X, Bi H, Zhao Z. Combined Use of Autologous Stromal Vascular Fraction Cells and Platelet-Rich Plasma for Chronic Ulceration of the Diabetic Lower Limb Improves Wound Healing. INT J LOW EXTR WOUND 2020; 20:135-142. [PMID: 32131655 DOI: 10.1177/1534734620907978] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The discovery of stromal vascular fraction cells and platelet-rich plasma in promoting tissue regeneration has prompted a new idea for the treatment of chronic diabetic ulcer of the lower limb. The study aim was to evaluate the clinical efficacy of a new method that applied stromal vascular fraction cells and platelet-rich plasma together in the treatment of recalcitrant chronic diabetic ulcer. We conducted a single-center, prospective, open, noncontrolled study. Four patients (5 ulcers in total) who had received standard treatment for diabetic ulcer for at least 3 months that failed to heal was enrolled. All patients were treated with surgical debridement, cell suspension (stromal vascular fraction cells suspended by platelet-rich plasma) injection into the wound, and platelet-rich plasma gel coverage. Wounds were measured every week after treatment using a 2-dimensional digital camera and a 3-dimensional wound measurement device. All patients were followed-up for 4 months after the treatment. Four of the 5 ulcers healed completely within a mean of 71.75 ± 29.57 days. The average proportion of granulation tissue achieved 100% within 4 weeks for all cases. The wound size decreased to less than half of the original size for all cases 4 weeks after the treatment. Findings revealed that the new treatment is efficient to achieve wound healing in patients with recalcitrant chronic diabetic ulcer of lower limb.
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Affiliation(s)
- Shilu Yin
- Department of Plastic Surgery, Peking University Third Hospital, Beijing, China
| | - Xin Yang
- Department of Plastic Surgery, Peking University Third Hospital, Beijing, China
| | - Hongsen Bi
- Department of Plastic Surgery, Peking University Third Hospital, Beijing, China
| | - Zhenmin Zhao
- Department of Plastic Surgery, Peking University Third Hospital, Beijing, China
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34
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Zhou X, Zhang F, Wang D, Wang J, Wang C, Xia K, Ying L, Huang X, Tao Y, Chen S, Xue D, Hua J, Liang C, Chen Q, Li F. Micro Fragmented Adipose Tissue Promotes the Matrix Synthesis Function of Nucleus Pulposus Cells and Regenerates Degenerated Intervertebral Disc in a Pig Model. Cell Transplant 2020; 29:963689720905798. [PMID: 32030997 PMCID: PMC7444234 DOI: 10.1177/0963689720905798] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Intervertebral disc (IVD) degeneration and consequent lower back pain is a common
disease. Micro fragmented adipose tissue (MFAT) is promising for a wide range of
applications in regenerative medicine. In this study, MFAT was isolated by a
nonenzymatic method and co-cultured with nucleus pulposus cells (NPCs) using an
indirect co-culture system in vitro. A pig disc degeneration
model was used to investigate the regenerative effect of MFAT on degenerated
IVDs in vivo. The mRNA expression of Sox9,
Acan, and Col2 in NPCs was significantly
increased, while no significant increase was observed in the mRNA expression of
proinflammatory cytokine genes after the NPCs were co-cultured with MFAT.
Nucleus pulposus (NP)-specific markers were increased in MFAT cells after
co-culture with NPCs. After injection of MFAT, the disc height, water content,
extracellular matrix, and structure of the degenerated NP were significantly
improved. MFAT promoted the matrix synthesis function of NPCs, and NPCs
stimulated the NP-like differentiation of MFAT cells. In addition, MFAT also
partly regenerated degenerated IVDs in the pig model.
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Affiliation(s)
- Xiaopeng Zhou
- Department of Orthopedics Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People's Republic of China.,Department of Orthopedics Research Institute of Zhejiang University, Hangzhou, Zhejiang, People's Republic of China.,These authors contributed equally to this article
| | - Feng Zhang
- Department of Orthopedics Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People's Republic of China.,Department of Orthopedics Research Institute of Zhejiang University, Hangzhou, Zhejiang, People's Republic of China.,These authors contributed equally to this article
| | - Dawei Wang
- Department of Orthopedics Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People's Republic of China.,These authors contributed equally to this article
| | - Jingkai Wang
- Department of Orthopedics Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People's Republic of China.,Department of Orthopedics Research Institute of Zhejiang University, Hangzhou, Zhejiang, People's Republic of China.,These authors contributed equally to this article
| | - Chenggui Wang
- Department of Orthopedics Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People's Republic of China.,Department of Orthopedics Research Institute of Zhejiang University, Hangzhou, Zhejiang, People's Republic of China
| | - Kaishun Xia
- Department of Orthopedics Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People's Republic of China.,Department of Orthopedics Research Institute of Zhejiang University, Hangzhou, Zhejiang, People's Republic of China
| | - Liwei Ying
- Department of Orthopedics Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People's Republic of China.,Department of Orthopedics Research Institute of Zhejiang University, Hangzhou, Zhejiang, People's Republic of China
| | - Xianpeng Huang
- Department of Orthopedics Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People's Republic of China.,Department of Orthopedics Research Institute of Zhejiang University, Hangzhou, Zhejiang, People's Republic of China
| | - Yiqing Tao
- Department of Orthopedics Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People's Republic of China.,Department of Orthopedics Research Institute of Zhejiang University, Hangzhou, Zhejiang, People's Republic of China
| | - Shouyong Chen
- Department of Orthopedics Surgery, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang, People's Republic of China
| | - Deting Xue
- Department of Orthopedics Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People's Republic of China.,Department of Orthopedics Research Institute of Zhejiang University, Hangzhou, Zhejiang, People's Republic of China
| | - Jianming Hua
- Department of Radiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People's Republic of China
| | - Chengzhen Liang
- Department of Orthopedics Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People's Republic of China.,Department of Orthopedics Research Institute of Zhejiang University, Hangzhou, Zhejiang, People's Republic of China
| | - Qixin Chen
- Department of Orthopedics Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People's Republic of China.,Department of Orthopedics Research Institute of Zhejiang University, Hangzhou, Zhejiang, People's Republic of China
| | - Fangcai Li
- Department of Orthopedics Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People's Republic of China.,Department of Orthopedics Research Institute of Zhejiang University, Hangzhou, Zhejiang, People's Republic of China
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Sun Y, Chen S, Zhang X, Pei M. Significance of Cellular Cross-Talk in Stromal Vascular Fraction of Adipose Tissue in Neovascularization. Arterioscler Thromb Vasc Biol 2020; 39:1034-1044. [PMID: 31018663 DOI: 10.1161/atvbaha.119.312425] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Adult stem cell-based therapy has been regarded as a promising treatment for tissue ischemia because of its ability to promote new blood vessel formation. Bone marrow-derived mesenchymal stem cells are the most used angiogenic cells for therapeutic neovascularization, yet the side effects and low efficacy have limited their clinical application. Adipose stromal vascular fraction is an easily accessible, heterogeneous cell system comprised of endothelial, stromal, and hematopoietic cell lineages, which has been shown to spontaneously form robust, patent, and functional vasculatures in vivo. However, the characteristics of each cell population and their specific roles in neovascularization remain an area of ongoing investigation. In this review, we summarize the functional capabilities of various stromal vascular fraction constituents during the process of neovascularization and attempt to analyze whether the cross-talk between these constituents generates a synergetic effect, thus contributing to the development of new potential therapeutic strategies to promote neovascularization.
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Affiliation(s)
- Yuan Sun
- From the Department of Vascular Surgery, Clinical Medical College of Yangzhou University, Subei People's Hospital of Jiangsu Province, Jiangsu, China (Y.S., X.Z.); Stem Cell and Tissue Engineering Laboratory, Department of Orthopaedics (Y.S., M.P.), Exercise Physiology (M.P.), and WVU Cancer Institute, Robert C. Byrd Health Sciences Center (M.P.), West Virginia University, Morgantown; and Department of Orthopaedics, Chengdu Military General Hospital, Chengdu, Sichuan, China (S.C.)
| | - Song Chen
- From the Department of Vascular Surgery, Clinical Medical College of Yangzhou University, Subei People's Hospital of Jiangsu Province, Jiangsu, China (Y.S., X.Z.); Stem Cell and Tissue Engineering Laboratory, Department of Orthopaedics (Y.S., M.P.), Exercise Physiology (M.P.), and WVU Cancer Institute, Robert C. Byrd Health Sciences Center (M.P.), West Virginia University, Morgantown; and Department of Orthopaedics, Chengdu Military General Hospital, Chengdu, Sichuan, China (S.C.)
| | - Xicheng Zhang
- From the Department of Vascular Surgery, Clinical Medical College of Yangzhou University, Subei People's Hospital of Jiangsu Province, Jiangsu, China (Y.S., X.Z.); Stem Cell and Tissue Engineering Laboratory, Department of Orthopaedics (Y.S., M.P.), Exercise Physiology (M.P.), and WVU Cancer Institute, Robert C. Byrd Health Sciences Center (M.P.), West Virginia University, Morgantown; and Department of Orthopaedics, Chengdu Military General Hospital, Chengdu, Sichuan, China (S.C.)
| | - Ming Pei
- From the Department of Vascular Surgery, Clinical Medical College of Yangzhou University, Subei People's Hospital of Jiangsu Province, Jiangsu, China (Y.S., X.Z.); Stem Cell and Tissue Engineering Laboratory, Department of Orthopaedics (Y.S., M.P.), Exercise Physiology (M.P.), and WVU Cancer Institute, Robert C. Byrd Health Sciences Center (M.P.), West Virginia University, Morgantown; and Department of Orthopaedics, Chengdu Military General Hospital, Chengdu, Sichuan, China (S.C.)
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Zhao F, Zhou L, Liu J, Xu Z, Ping W, Li H, Xu L, Xu Z, Zhou C, Wang M, Jia R. Construction of a vascularized bladder with autologous adipose-derived stromal vascular fraction cells combined with bladder acellular matrix via tissue engineering. J Tissue Eng 2019; 10:2041731419891256. [PMID: 31827758 PMCID: PMC6886281 DOI: 10.1177/2041731419891256] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2019] [Accepted: 11/06/2019] [Indexed: 11/17/2022] Open
Abstract
The formation of an effective vascular network can promote peripheral angiogenesis, ensuring an effective supply of blood, oxygen, and nutrients to an engineered bladder, which is important for bladder tissue engineering. Stromal vascular fraction cells (SVFs) promote vascularization and improve the function of injured tissues. In this study, adipose tissue-derived SVFs were introduced as an angiogenic cell source and seeded into the bladder acellular matrix (BAM) to generate a SVF-BAM complex for bladder reconstruction. The morphological regeneration and functional restoration of the engineered bladder were evaluated. In addition, we also explored the role of the Wnt5a/sFlt-1 noncanonical Wnt signaling pathway in regulating the angiogenesis of SVFs, and in maintaining the rational capability of SVFs to differentiate into vasculature in regenerated tissues. Histological assessment indicated that the SVF-BAM complex was more effective in promoting smooth muscle, vascular, and nerve regeneration than BAM alone and subsequently led to the restoration of bladder volume and bladder compliance. Moreover, exogenous Wnt5a was able to enhance angiogenesis by increasing the activity of MMP2, MMP9, and VEGFR2. Simultaneously, the expression of sFlt-1 was also increased, which enhanced the stability of the SVFs angiogenic capability. SVFs may be a potential cell source for tissue-engineered bladders. The Wnt5a/sFlt-1 pathway is involved in the regulation of autologous vascular formation by SVFs. The rational regulation of this pathway can promote neo-microvascularization in tissue-engineered bladders.
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Affiliation(s)
- Feng Zhao
- Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Liuhua Zhou
- Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Jingyu Liu
- Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Zhongle Xu
- Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.,Department of Urology, Hefei Hospital Affiliated to Anhui Medical University (The Second People's Hospital of Hefei), Hefei, China
| | - Wenwen Ping
- Department of Rheumatology, Zhongda Hospital, Medical School of Southeast University, Nanjing, China
| | - Haiyang Li
- Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Luwei Xu
- Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Zheng Xu
- Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Changcheng Zhou
- Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Min Wang
- Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Ruipeng Jia
- Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
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Haenel A, Ghosn M, Karimi T, Vykoukal J, Shah D, Valderrabano M, Schulz DG, Raizner A, Schmitz C, Alt EU. Unmodified autologous stem cells at point of care for chronic myocardial infarction. World J Stem Cells 2019; 11:831-858. [PMID: 31692971 PMCID: PMC6828597 DOI: 10.4252/wjsc.v11.i10.831] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2019] [Revised: 06/03/2019] [Accepted: 08/27/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Numerous studies investigated cell-based therapies for myocardial infarction (MI). The conflicting results of these studies have established the need for developing innovative approaches for applying cell-based therapy for MI. Experimental studies on animal models demonstrated the potential of fresh, uncultured, unmodified, autologous adipose-derived regenerative cells (UA-ADRCs) for treating acute MI. In contrast, studies on the treatment of chronic MI (CMI; > 4 wk post-MI) with UA-ADRCs have not been published so far. Among several methods for delivering cells to the myocardium, retrograde delivery into a temporarily blocked coronary vein has recently been demonstrated as an effective option.
AIM To test the hypothesis that in experimentally-induced chronic myocardial infarction (CMI; > 4 wk post-MI) in pigs, retrograde delivery of fresh, uncultured, unmodified, autologous adipose-derived regenerative cells (UA-ADRCs) into a temporarily blocked coronary vein improves cardiac function and structure.
METHODS The left anterior descending (LAD) coronary artery of pigs was blocked for 180 min at time point T0. Then, either 18 × 106 UA-ADRCs prepared at “point of care” or saline as control were retrogradely delivered via an over-the-wire balloon catheter placed in the temporarily blocked LAD vein 4 wk after T0 (T1). Effects of cells or saline were assessed by cardiac magnetic resonance (CMR) imaging, late gadolinium enhancement CMR imaging, and post mortem histologic analysis 10 wk after T0 (T2).
RESULTS Unlike the delivery of saline, delivery of UA-ADRCs demonstrated statistically significant improvements in cardiac function and structure at T2 compared to T1 (all values given as mean ± SE): Increased mean LVEF (UA-ADRCs group: 34.3% ± 2.9% at T1 vs 40.4 ± 2.6% at T2, P = 0.037; saline group: 37.8% ± 2.6% at T1 vs 36.2% ± 2.4% at T2, P > 0.999), increased mean cardiac output (UA-ADRCs group: 2.7 ± 0.2 L/min at T1 vs 3.8 ± 0.2 L/min at T2, P = 0.002; saline group: 3.4 ± 0.3 L/min at T1 vs 3.6 ± 0.3 L/min at T2, P = 0.798), increased mean mass of the left ventricle (UA-ADRCs group: 55.3 ± 5.0 g at T1 vs 71.3 ± 4.5 g at T2, P < 0.001; saline group: 63.2 ± 3.4 g at T1 vs 68.4 ± 4.0 g at T2, P = 0.321) and reduced mean relative amount of scar volume of the left ventricular wall (UA-ADRCs group: 20.9% ± 2.3% at T1 vs 16.6% ± 1.2% at T2, P = 0.042; saline group: 17.6% ± 1.4% at T1 vs 22.7% ± 1.8% at T2, P = 0.022).
CONCLUSION Retrograde cell delivery of UA-ADRCs in a porcine model for the study of CMI significantly improved myocardial function, increased myocardial mass and reduced the formation of scar tissue.
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Affiliation(s)
- Alexander Haenel
- Heart and Vascular Institute, Department of Medicine, Tulane University Health Science Center, New Orleans, LA 70112, United States
- The Methodist Hospital Research Institute, Houston, TX 77030, United States
- Department of Radiology and Nuclear Medicine, University Hospital Schleswig-Holstein, Lübeck D-23562, Germany
| | - Mohamad Ghosn
- Houston Methodist DeBakey Heart and Vascular Center, Houston, TX 77030, United States
| | - Tahereh Karimi
- Heart and Vascular Institute, Department of Medicine, Tulane University Health Science Center, New Orleans, LA 70112, United States
| | - Jody Vykoukal
- Department of Translational Molecular Pathology, MD Anderson Cancer Center, The University of Texas, Houston, TX 77030, United States
| | - Dipan Shah
- Houston Methodist DeBakey Heart and Vascular Center, Houston, TX 77030, United States
| | - Miguel Valderrabano
- Houston Methodist DeBakey Heart and Vascular Center, Houston, TX 77030, United States
| | - Daryl G Schulz
- The Methodist Hospital Research Institute, Houston, TX 77030, United States
| | - Albert Raizner
- Houston Methodist DeBakey Heart and Vascular Center, Houston, TX 77030, United States
| | - Christoph Schmitz
- Institute of Anatomy, Faculty of Medicine, LMU Munich, Munich D-80336, Germany
| | - Eckhard U Alt
- Heart and Vascular Institute, Department of Medicine, Tulane University Health Science Center, New Orleans, LA 70112, United States
- The Methodist Hospital Research Institute, Houston, TX 77030, United States
- Isar Klinikum Munich, Munich D-80331, Germany
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Choi JW, Moon H, Jung SE, Lim S, Lee S, Kim IK, Lee HB, Lee J, Song BW, Kim SW, Hwang KC. Hypoxia Rapidly Induces the Expression of Cardiomyogenic Factors in Human Adipose-Derived Adherent Stromal Cells. J Clin Med 2019; 8:E1231. [PMID: 31443313 PMCID: PMC6723458 DOI: 10.3390/jcm8081231] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2019] [Revised: 08/12/2019] [Accepted: 08/15/2019] [Indexed: 11/27/2022] Open
Abstract
BACKGROUND The efficacy of interstitial vascular fraction (SVF) transplantation in the treatment of heart disease has been proven in a variety of in vivo studies. In a previous study, we found that bone marrow-derived mesenchymal stem cells (BM-MSCs) altered their expression of several cardiomyogenic factors under hypoxic conditions. METHODS We hypothesized that hypoxia may also induce obtained adipose-derived adherent stromal cells (ADASs) from SVFs and adipose-derived stem cells (ASCs) to differentiate into cardiomyocytes and/or cells with comparable phenotypes. We examined the differentiation markers of cell lineages in ADASs and ASCs according to time by hypoxic stress and found that only ADASs expressed cardiomyogenic markers within 24 h under hypoxic conditions in association with the expression of hypoxia-inducible factor 1-α (HIF-1α). RESULTS Differentially secreted proteins in a conditioned medium (CM) from ASCs and ADASs under normoxic or hypoxic conditions were detected using an antibody assay and may be associated with a dramatic increase in the expression of cardiomyogenic markers in only ADASs. Furthermore, the cardiomyogenic factors were expressed more rapidly in ADASs than in ASCs under hypoxic conditions in association with the expression of HIF-1α, and angiogenin, fibroblast growth factor-19 (FGF-19) and/or macrophage inhibitory factor (MIF) are related. CONCLUSIONS These results provide new insights into the applicability of ADASs preconditioned by hypoxic stress in cardiac diseases.
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Affiliation(s)
- Jung-Won Choi
- Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung-si, Gangwon-do 210-701, Korea
| | - Hanbyeol Moon
- Department of Integrated Omics for Biomedical Sciences, Graduate School, Yonsei University, Seoul 03722, Korea
| | - Seung Eun Jung
- Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung-si, Gangwon-do 210-701, Korea
| | - Soyeon Lim
- Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung-si, Gangwon-do 210-701, Korea
- International St. Mary's Hospital, Catholic Kwandong University, Incheon Metropolitan City 22711, Korea
| | - Seahyoung Lee
- Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung-si, Gangwon-do 210-701, Korea
- International St. Mary's Hospital, Catholic Kwandong University, Incheon Metropolitan City 22711, Korea
| | - Il-Kwon Kim
- Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung-si, Gangwon-do 210-701, Korea
- International St. Mary's Hospital, Catholic Kwandong University, Incheon Metropolitan City 22711, Korea
| | - Hoon-Bum Lee
- Department of Plastic and Reconstructive Surgery, International St. Mary's Hospital, Catholic Kwandong University, Incheon Metropolitan City 22711, Korea
| | - Jiyun Lee
- Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung-si, Gangwon-do 210-701, Korea
| | - Byeong-Wook Song
- Department of Medical Science, College of Medicine, Catholic Kwandong University, Gangneung-si, Gangwon-do 25601, Korea
| | - Sang Woo Kim
- Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung-si, Gangwon-do 210-701, Korea.
- International St. Mary's Hospital, Catholic Kwandong University, Incheon Metropolitan City 22711, Korea.
| | - Ki-Chul Hwang
- Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung-si, Gangwon-do 210-701, Korea.
- International St. Mary's Hospital, Catholic Kwandong University, Incheon Metropolitan City 22711, Korea.
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Tran TDX, Wu CM, Dubey NK, Deng YH, Su CW, Pham TT, Thi Le PB, Sestili P, Deng WP. Time- and Kellgren⁻Lawrence Grade-Dependent Changes in Intra-Articularly Transplanted Stromal Vascular Fraction in Osteoarthritic Patients. Cells 2019; 8:E308. [PMID: 30987218 PMCID: PMC6523621 DOI: 10.3390/cells8040308] [Citation(s) in RCA: 39] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2019] [Revised: 03/29/2019] [Accepted: 04/01/2019] [Indexed: 12/13/2022] Open
Abstract
Knee osteoarthritis (OA) is one of the most prevalent disorders in elderly population. Among various therapeutic alternatives, we employed stromal vascular fraction (SVF), a heterogeneous cell population, to regenerate damaged knee cartilage. OA patients were classified on the basis of age, gender, body mass index (BMI), and x-ray-derived Kellgren-Lawrence (KL) grade. They were treated with SVF and followed-up for 24 months. Visual analogue scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index were used to determine treatment efficacy. Cartilage healing was assessed using the MRI-based Outerbridge score (OS) and evaluation of bone marrow edema (BME) lesions, while a placebo group was used as a control. Time- and KL-dependent changes were also monitored. We observed a decreasing trend in VAS score and WOMAC index in the SVF-treated group up to 24 months, as compared with the placebo group. Besides, a significant increase and decrease in Lysholm and OS, respectively, were observed in the treatment group. Compared with the values before treatment, the greatly reduced WOMAC scores of KL3 than KL2 groups at 24 months, indicate more improvement in the KL3 group. Highly decreased BME in the treated group was also noted. In conclusion, the SVF therapy is effective in the recovery of OA patients of KL3 grade in 24 months.
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Affiliation(s)
- Tung Dang Xuan Tran
- School of Dentistry, Taipei Medical University, Taipei 11031, Taiwan.
- Van Hanh Stem Cells Unit, Van Hanh Hospital, Ho Chi Minh City 700000, Vietnam.
| | - Chi-Ming Wu
- Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei 11031, Taiwan.
| | - Navneet Kumar Dubey
- Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei 11031, Taiwan.
- Stem Cell Research Center, College of Oral Medicine, Taipei Medical University, Taipei 11031, Taiwan.
| | - Yue-Hua Deng
- Department of Life Science, Fu Jen Catholic University, New Taipei City 242, Taiwan.
| | - Chun-Wei Su
- Stem Cell Research Center, College of Oral Medicine, Taipei Medical University, Taipei 11031, Taiwan.
| | - Tu Thanh Pham
- Van Hanh Stem Cells Unit, Van Hanh Hospital, Ho Chi Minh City 700000, Vietnam.
| | - Phuong Bich Thi Le
- Department of Pulmonary Medicine, Vietnam Military Medical Academy, Ha Noi 12108, Vietnam.
| | - Piero Sestili
- Dipartimento di Scienze Biomolecolari, Università degli Studi di Urbino Carlo Bo Via "I Maggetti" 26, 61029 Urbino, Italy.
| | - Win-Ping Deng
- School of Dentistry, Taipei Medical University, Taipei 11031, Taiwan.
- Stem Cell Research Center, College of Oral Medicine, Taipei Medical University, Taipei 11031, Taiwan.
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Choi SA, Chong S, Kwak PA, Moon YJ, Jangra A, Phi JH, Lee JY, Park SH, Kim SK. Impaired functional recovery of endothelial colony-forming cells from moyamoya disease in a chronic cerebral hypoperfusion rat model. J Neurosurg Pediatr 2019; 23:204-213. [PMID: 30668528 DOI: 10.3171/2018.8.peds1883] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2018] [Accepted: 08/06/2021] [Indexed: 11/06/2022]
Abstract
OBJECTIVEEndothelial colony-forming cells (ECFCs) isolated from pediatric patients with moyamoya disease (MMD) have demonstrated decreased numbers and defective functioning in in vitro experiments. However, the function of ECFCs has not been evaluated using in vivo animal models. In this study, the authors compared normal and MMD ECFCs using a chronic cerebral hypoperfusion (CCH) rat model.METHODSA CCH rat model was made via ligation of the bilateral common carotid arteries (2-vessel occlusion [2-VO]). The rats were divided into three experimental groups: vehicle-treated (n = 8), normal ECFC-treated (n = 8), and MMD ECFC-treated (n = 8). ECFCs were injected into the cisterna magna. A laser Doppler flowmeter was used to evaluate cerebral blood flow, and a radial arm maze test was used to examine cognitive function. Neuropathological examinations of the hippocampus and agranular cortex were performed using hematoxylin and eosin and Luxol fast blue staining in addition to immunofluorescence with CD31, von Willebrand factor, NeuN, myelin basic protein, glial fibrillary acidic protein, and cleaved caspase-3 antibodies.RESULTSThe normal ECFC-treated group exhibited improvement in the restoration of cerebral perfusion and in behavior compared with the vehicle-treated and MMD ECFC-treated groups at the 12-week follow-up after the 2-VO surgery. The normal ECFC-treated group showed a greater amount of neovasculogenesis and neurogenesis, with less apoptosis, than the other groups.CONCLUSIONSThese results support the impaired functional recovery of MMD ECFCs compared with normal ECFCs in a CCH rat model. This in vivo study suggests the functional role of ECFCs in the pathogenesis of MMD.
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Affiliation(s)
- Seung Ah Choi
- 1Division of Pediatric Neurosurgery, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital
- 2Department of Neurosurgery, Seoul National University Hospital, Seoul National University College of Medicine
| | - Sangjoon Chong
- 1Division of Pediatric Neurosurgery, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital
- 2Department of Neurosurgery, Seoul National University Hospital, Seoul National University College of Medicine
| | - Pil Ae Kwak
- 1Division of Pediatric Neurosurgery, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital
- 2Department of Neurosurgery, Seoul National University Hospital, Seoul National University College of Medicine
| | - Youn Joo Moon
- 1Division of Pediatric Neurosurgery, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital
- 2Department of Neurosurgery, Seoul National University Hospital, Seoul National University College of Medicine
| | - Anshika Jangra
- 1Division of Pediatric Neurosurgery, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital
- 2Department of Neurosurgery, Seoul National University Hospital, Seoul National University College of Medicine
| | - Ji Hoon Phi
- 1Division of Pediatric Neurosurgery, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital
- 2Department of Neurosurgery, Seoul National University Hospital, Seoul National University College of Medicine
| | - Ji Yeoun Lee
- 1Division of Pediatric Neurosurgery, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital
- 2Department of Neurosurgery, Seoul National University Hospital, Seoul National University College of Medicine
- 3Department of Anatomy, Seoul National University College of Medicine; and
| | - Sung-Hye Park
- 4Department of Pathology, Seoul National University Hospital, Seoul, Korea
| | - Seung-Ki Kim
- 1Division of Pediatric Neurosurgery, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital
- 2Department of Neurosurgery, Seoul National University Hospital, Seoul National University College of Medicine
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Liposuction Aspirate Fluid Adipose-Derived Stem Cell Injection and Secondary Healing in Fingertip Injury: A Pilot Study. Plast Reconstr Surg 2018; 142:136-147. [PMID: 29649060 DOI: 10.1097/prs.0000000000004506] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
BACKGROUND Although fingertip injuries account for a high proportion of trauma patients, the correct surgical approach is still debated. The authors compared the traditional conservative approach and a new treatment based on the injection of liposuction aspirate fluid. METHODS Forty consecutive patients with a fingertip injury were dichotomized into group A (control group; conservative approach) and group B (treatment group). Group B underwent liposuction, followed by filtration of the lipoaspirate in a closed device (MyStem EVO kit), allowing the nonenzymatic separation of liposuction aspirate fluid, which was then injected at the site of injury. Objective outcomes were time for healing, strength, mobility of joint, and touch and sensory function. Subjective outcomes were cold intolerance, pain, hand disability, and aesthetic result. An aliquot of liposuction aspirate fluid was sent to the laboratory for cellular isolation and analysis by flow cytometry and in vitro differentiation assays. RESULTS The average healing time was 22.3 days in group B and 24.9 days in group A (p < 0.05). Eighty-five percent of group B patients and 67 percent of group A patients scored normal to diminished superficial sensibility (p < 0.05). Group A had higher pain and cold intolerance scores (p < 0.05). Group B scored greater aesthetic and disabilities outcome results (p < 0.05). The cell isolation yield was 8.3 × 10(5)/ml, with a percentage of viable cells of 74.3 percent. Flow cytometry identified a mesenchymal immunophenotype, and in vitro osteogenic and adipogenic induction confirmed the bilinear potential of the isolated cells. CONCLUSION This clinical study demonstrates for the first time the regenerative potential of liposuction aspirate fluid adipose-derived stem cells in a clinical application. CLINICAL QUESTION/LEVEL OF EVIDENCE Therapeutic, II.
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Später T, Frueh FS, Nickels RM, Menger MD, Laschke MW. Prevascularization of collagen-glycosaminoglycan scaffolds: stromal vascular fraction versus adipose tissue-derived microvascular fragments. J Biol Eng 2018; 12:24. [PMID: 30473729 PMCID: PMC6234670 DOI: 10.1186/s13036-018-0118-3] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2018] [Accepted: 10/31/2018] [Indexed: 02/06/2023] Open
Abstract
Background The seeding of scaffolds with the stromal vascular fraction (SVF) of adipose tissue is a common prevascularization strategy in tissue engineering. Alternatively, adipose tissue-derived microvascular fragments (ad-MVF) may serve as vascularization units. In contrast to SVF single cells, they represent a mixture of intact arteriolar, capillary and venular vessel segments. Therefore, we herein hypothesized that the ad-MVF-based prevascularization of scaffolds is superior to the conventional SVF single cells-based approach. Results SVF single cells and ad-MVF were enzymatically isolated from epididymal fat pads of green fluorescent protein (GFP)+ donor mice to assess their viability and cellular composition using fluorescence microscopy and flow cytometry. Moreover, collagen-glycosaminoglycan matrices (Integra®) were seeded with identical amounts of the isolates and implanted into full-thickness skin defects within dorsal skinfold chambers of GFP− recipient mice for the intravital fluorescent microscopic, histological and immunohistochemical analysis of implant vascularization and incorporation throughout an observation period of 2 weeks. Non-seeded matrices served as controls. While both isolates contained a comparable fraction of endothelial cells, perivascular cells, adipocytes and stem cells, ad-MVF exhibited a significantly higher viability. After in vivo implantation, the vascularization of ad-MVF-seeded scaffolds was improved when compared to SVF-seeded ones, as indicated by a significantly higher functional microvessel density. This was associated with an enhanced cellular infiltration, collagen content and density of CD31+/GFP+ microvessels particularly in the center of the implants, demonstrating a better incorporation into the surrounding host tissue. In contrast, non-seeded matrices exhibited a poor vascularization, incorporation and epithelialization over time. Conclusions The present study demonstrates that ad-MVF are highly potent vascularization units that markedly accelerate and improve scaffold vascularization when compared to the SVF. Electronic supplementary material The online version of this article (10.1186/s13036-018-0118-3) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Thomas Später
- 1Institute for Clinical & Experimental Surgery, Saarland University, 66421 Homburg/Saar, Germany
| | - Florian S Frueh
- Division of Plastic Surgery and Hand Surgery, University Hospital Zürich, University of Zürich, 8091 Zürich, Switzerland
| | - Ruth M Nickels
- 1Institute for Clinical & Experimental Surgery, Saarland University, 66421 Homburg/Saar, Germany
| | - Michael D Menger
- 1Institute for Clinical & Experimental Surgery, Saarland University, 66421 Homburg/Saar, Germany
| | - Matthias W Laschke
- 1Institute for Clinical & Experimental Surgery, Saarland University, 66421 Homburg/Saar, Germany
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StemBell therapy stabilizes atherosclerotic plaques after myocardial infarction. Cytotherapy 2018; 20:1143-1154. [DOI: 10.1016/j.jcyt.2018.05.006] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2017] [Revised: 05/11/2018] [Accepted: 05/14/2018] [Indexed: 01/10/2023]
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Wysoczynski M, Khan A, Bolli R. New Paradigms in Cell Therapy: Repeated Dosing, Intravenous Delivery, Immunomodulatory Actions, and New Cell Types. Circ Res 2018; 123:138-158. [PMID: 29976684 PMCID: PMC6050028 DOI: 10.1161/circresaha.118.313251] [Citation(s) in RCA: 113] [Impact Index Per Article: 16.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Perhaps the most important advance in the field of cell therapy for heart disease has been the recognition that all stem/progenitor cells (both adult and embryonic) fail to engraft in the heart to a significant extent and thus work via paracrine mechanisms. This fundamental advance has led to 4 new paradigms that are discussed in this review and that may importantly shape, or even revolutionize, the future of the field: (1) repeated cell therapy, (2) intravenous cell therapy, (3) immunomodulatory actions of cell therapy, and (4) new cell types. Because virtually all of our current knowledge of cell therapy is predicated on the effects of a single cell dose, the idea that the full therapeutic effects of a cell product require repeated doses is disruptive and has far-reaching implications. For example, inadequate dosing (single-dose protocols) may be responsible, at least in part, for the borderline or disappointing results obtained to date in clinical trials; furthermore, future studies (both preclinical and clinical) may need to incorporate repeated cell administrations. Another disruptive idea, supported by emerging preclinical and clinical evidence, is that intravenously injected cells can produce beneficial effects on the heart, presumably via release of paracrine factors in extracardiac organs or endocrine factors into the systemic circulation. Intravenous administration would obviate the need for direct delivery of cells to the heart, making cell therapy simpler, cheaper, safer, more scalable, and more broadly available, even on an outpatient basis. Although the mechanism of action of cell therapy remains elusive, there is compelling in vitro evidence that transplanted cells modulate the function of various immune cell types via release of paracrine factors, such as extracellular vesicles, although in vivo evidence is still limited. Investigation of the new paradigms reviewed herein should be a top priority because it may profoundly transform cell therapy and finally make it a reality.
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Affiliation(s)
- Marcin Wysoczynski
- From the Institute of Molecular Cardiology, University of Louisville, KY
| | - Abdur Khan
- From the Institute of Molecular Cardiology, University of Louisville, KY
| | - Roberto Bolli
- From the Institute of Molecular Cardiology, University of Louisville, KY.
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Shin S, Choi JW, Lim S, Lee S, Jun EY, Sun HM, Kim IK, Lee HB, Kim SW, Hwang KC. Anti-apoptotic effects of adipose-derived adherent stromal cells in mesenchymal stem cells exposed to oxidative stress. Cell Biochem Funct 2018; 36:263-272. [PMID: 29920999 DOI: 10.1002/cbf.3338] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2018] [Revised: 02/22/2018] [Accepted: 05/23/2018] [Indexed: 01/28/2023]
Abstract
Adipose-derived stromal vascular fractions (SVFs) are a heterogeneous collection of cells, and their regenerative modality has been applied in various animal experiments and clinical trials. Despite the attractive advantages of SVFs in clinical interventions, the recent status of clinical studies involving the application of SVFs in many diseases has not been fully evaluated. Mesenchymal stem cells (MSCs) are multipotent stromal cells that can differentiate into a variety of cell types despite their low numbers in heart tissue. Here, we sought to determine if SVF implantation into impaired heart tissue affected endogenous MSCs in the heart. Therefore, we investigated the expression levels of proteins associated with oxidation, inflammation, and apoptosis in MSCs co-cultured with adipose-derived adherent stromal cells (ADASs) from 6 donors' SVFs under oxidative stress conditions for their roles in many physiological processes in the heart. Interestingly, p53 pathway proteins and mitogen-activated protein kinase (MAPK) signalling pathway components were up-regulated by H2 O2 but exhibited a downward trend in MSCs co-cultured with ADASs. These data suggest that ADASs may inhibit oxidative stress-induced apoptosis in MSCs via the p53 and MAPK pathways. Our findings also suggest that the positive effects of SVF implantation into damaged heart tissue may be attributed to the various responses of MSCs. This finding may provide new insights for the clinical application of adipose-derived SVF transplantation in cardiac diseases. SIGNIFICANCE OF THE STUDY We investigated the expression levels of proteins associated with oxidation, inflammation, and apoptosis in MSCs co-cultured with isolated ADASs from 6 donors' SVFs under oxidative stress conditions. Our results imply that isolated ADASs from SVFs may inhibit oxidative stress-induced cell cycle arrest and/or apoptosis in MSCs via a p53-dependent pathway. Furthermore, we identified an anti-apoptotic mechanism involving oxidative stress-induced apoptosis by adipose-derived ADASs in MSCs for the first time. Our findings suggest that the positive effects of SVF implantation into damaged heart tissue may be attributed to the various actions of MSCs.
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Affiliation(s)
- Sunhye Shin
- Department of Integrated Omics for Biomedical Sciences, Graduate School, Yonsei University, Seoul, Republic of Korea
| | - Jung-Won Choi
- Department of Health and Environment, College of Engineering, Catholic Kwandong University, Gangneung-si, Gangwon-do, Republic of Korea.,Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung-si, Gangwon-do, Republic of Korea
| | - Soyeon Lim
- Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung-si, Gangwon-do, Republic of Korea.,International St. Mary's Hospital, Catholic Kwandong University, Incheon, Republic of Korea
| | - Seahyoung Lee
- Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung-si, Gangwon-do, Republic of Korea.,International St. Mary's Hospital, Catholic Kwandong University, Incheon, Republic of Korea
| | - Eun-Young Jun
- Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung-si, Gangwon-do, Republic of Korea.,Cell Therapy Center, Catholic Kwandong University International St. Mary's Hospital, Incheon, Republic of Korea
| | - Hyun-Min Sun
- Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung-si, Gangwon-do, Republic of Korea.,Cell Therapy Center, Catholic Kwandong University International St. Mary's Hospital, Incheon, Republic of Korea
| | - Il-Kwon Kim
- Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung-si, Gangwon-do, Republic of Korea.,Cell Therapy Center, Catholic Kwandong University International St. Mary's Hospital, Incheon, Republic of Korea
| | - Hoon-Bum Lee
- Department of Plastic and Reconstructive Surgery, Catholic Kwandong University, International St. Mary's Hospital, Incheon, Republic of Korea
| | - Sang Woo Kim
- Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung-si, Gangwon-do, Republic of Korea.,International St. Mary's Hospital, Catholic Kwandong University, Incheon, Republic of Korea
| | - Ki-Chul Hwang
- Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung-si, Gangwon-do, Republic of Korea.,International St. Mary's Hospital, Catholic Kwandong University, Incheon, Republic of Korea
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Wu R, Hu X, Wang J. Concise Review: Optimized Strategies for Stem Cell-Based Therapy in Myocardial Repair: Clinical Translatability and Potential Limitation. Stem Cells 2018; 36:482-500. [PMID: 29330880 DOI: 10.1002/stem.2778] [Citation(s) in RCA: 58] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2017] [Revised: 12/28/2017] [Accepted: 12/31/2017] [Indexed: 12/15/2022]
Abstract
Ischemic heart diseases (IHDs) remain major public health problems with high rates of morbidity and mortality worldwide. Despite significant advances, current therapeutic approaches are unable to rescue the extensive and irreversible loss of cardiomyocytes caused by severe ischemia. Over the past 16 years, stem cell-based therapy has been recognized as an innovative strategy for cardiac repair/regeneration and functional recovery after IHDs. Although substantial preclinical animal studies using a variety of stem/progenitor cells have shown promising results, there is a tremendous degree of skepticism in the clinical community as many stem cell trials do not confer any beneficial effects. How to accelerate stem cell-based therapy toward successful clinical application attracts considerate attention. However, many important issues need to be fully addressed. In this Review, we have described and compared the effects of different types of stem cells with their dose, delivery routes, and timing that have been routinely tested in recent preclinical and clinical findings. We have also discussed the potential mechanisms of action of stem cells, and explored the role and underlying regulatory components of stem cell-derived secretomes/exosomes in myocardial repair. Furthermore, we have critically reviewed the different strategies for optimizing both donor stem cells and the target cardiac microenvironments to enhance the engraftment and efficacy of stem cells, highlighting their clinical translatability and potential limitation. Stem Cells 2018;36:482-500.
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Affiliation(s)
- Rongrong Wu
- Department of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China.,Cardiovascular Key Laboratory of Zhejiang Province, Hangzhou, People's Republic of China
| | - Xinyang Hu
- Department of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China.,Cardiovascular Key Laboratory of Zhejiang Province, Hangzhou, People's Republic of China
| | - Jian'an Wang
- Department of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China.,Cardiovascular Key Laboratory of Zhejiang Province, Hangzhou, People's Republic of China
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Nseir I, Delaunay F, Latrobe C, Bonmarchand A, Coquerel-Beghin D, Auquit-Auckbur I. Use of adipose tissue and stromal vascular fraction in hand surgery. Orthop Traumatol Surg Res 2017. [PMID: 28645702 DOI: 10.1016/j.otsr.2017.05.017] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
Adipose tissue is an abundant source of various cell types including not only adipocytes, but also progenitor and endothelial cells from thestroma. Interest in adipose tissue has surged since the identification in 2001 of adipose-derived stem cells (ADSCs) and of the stromal vascular fraction (SVF) obtained from adipose tissue by enzymatic digestion and centrifugation. SVF has been proven effective in ensuring tissue regeneration, thus improving tissue trophicityand vascularisation. These effects have generated strong interest among both physicians and surgeons, particularly in the field of hand surgery. Several applications have been developed and used, for instance to treat Dupuytren's contracture, systemic sclerosis-related hand lesions, and skin ageing at the hand. Other uses are being evaluated in clinical or animal studies. The objective of this article is to review the capabilities of adipose tissue and their current and potential applications in hand surgery.
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Affiliation(s)
- I Nseir
- Service de chirurgie plastique et chirurgie de la main, CHU de Rouen, 1, rue de Germont, 76000 Rouen, France.
| | - F Delaunay
- Service de chirurgie plastique et chirurgie de la main, CHU de Rouen, 1, rue de Germont, 76000 Rouen, France.
| | - C Latrobe
- Service de chirurgie orthopédique et traumatologique, CHU de Rouen, 1, rue de Germont, 76000 Rouen, France.
| | - A Bonmarchand
- Service de chirurgie plastique et chirurgie de la main, CHU de Rouen, 1, rue de Germont, 76000 Rouen, France.
| | - D Coquerel-Beghin
- Service de chirurgie plastique et chirurgie de la main, CHU de Rouen, 1, rue de Germont, 76000 Rouen, France.
| | - I Auquit-Auckbur
- Service de chirurgie plastique et chirurgie de la main, CHU de Rouen, 1, rue de Germont, 76000 Rouen, France.
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Nseir I, Delaunay F, Latrobe C, Bonmarchand A, Coquerel-Beghin D, Auquit-Auckbur I. Apport du tissu adipeux et de la fraction vasculaire stromale en chirurgie de la main. REVUE DE CHIRURGIE ORTHOPÉDIQUE ET TRAUMATOLOGIQUE 2017; 103:643-648. [DOI: 10.1016/j.rcot.2017.06.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Bora P, Majumdar AS. Adipose tissue-derived stromal vascular fraction in regenerative medicine: a brief review on biology and translation. Stem Cell Res Ther 2017; 8:145. [PMID: 28619097 PMCID: PMC5472998 DOI: 10.1186/s13287-017-0598-y] [Citation(s) in RCA: 312] [Impact Index Per Article: 39.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Adipose/fat tissue provides an abundant source of stromal vascular fraction (SVF) cells for immediate administration and can also give rise to a substantial number of cultured, multipotent adipose-derived stromal cells (ADSCs). Recently, both SVF and ADSCs have gained wide-ranging translational significance in regenerative medicine. Initially used for cosmetic breast enhancement, this mode of treatment has found use in many diseases involving immune disorders, tissue degeneration, and ischaemic conditions. In this review, we try to address several important aspects of this field, outlining the biology, technology, translation, and challenges related to SVF- and ADSC-based therapies. Starting from the basics of SVF and ADSC isolation, we touch upon recently developed technologies, addressing elements of novel methods and devices under development for point-of-care isolation of SVF. Characterisation of SVF cells and ADSCs is also an evolving area and we look into unusual expression of CD34 antigen as an interesting marker for such purposes. Based on reports involving different cells of the SVF, we draw a potential mode of action, focussing on angiogenesis since it involves multiple cells, unlike immunomodulation which is governed predominantly by ADSCs. We have looked into the latest research, experimental therapies, and clinical trials which are utilising SVF/ADSCs in conditions such as multiple sclerosis, Crohn’s disease, peripheral neuropathy, osteoarthritis, diabetic foot ulcer, and so forth. However, problems have arisen with regards to the lack of proper regulatory guidelines for such therapies and, since the introduction of US Food and Drug Administration draft guidelines and the Reliable and Effective Growth for Regenerative Health Options that Improve Wellness (REGROW) Act, the debate became more public with regards to safe and efficacious use of these cells.
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Affiliation(s)
- Pablo Bora
- Stempeutics Research Private Limited, Akshay Tech Park, # 72&73, 2nd Floor, EPIP Zone, Phase 1, Whitefield, Bangalore, 560066, India.,Present Address: Department of Molecular Biology & Genetics, Faculty of Science, Jihočeská univerzita v Českých Budějovicích (University of South Bohemia), Branišovská 31, 37005, České Budějovice, Czech Republic
| | - Anish S Majumdar
- Stempeutics Research Private Limited, Akshay Tech Park, # 72&73, 2nd Floor, EPIP Zone, Phase 1, Whitefield, Bangalore, 560066, India.
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Adipose Extracellular Matrix/Stromal Vascular Fraction Gel: A Novel Adipose Tissue-Derived Injectable for Stem Cell Therapy. Plast Reconstr Surg 2017; 139:867-879. [PMID: 28002250 DOI: 10.1097/prs.0000000000003214] [Citation(s) in RCA: 103] [Impact Index Per Article: 12.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND Adipose-derived stem cells and other stromal vascular fraction cells were used more often for stem cell therapy, even though limitations such as poor cell retention rate, complicated and expensive isolation processes, and the use of specific laboratory equipment need to be overcome. METHODS Here, the authors developed a novel but simple method for generating an injectable mixture of stromal vascular fraction cells and native adipose extracellular matrix. It is a purely mechanical process in which lipoaspirate is processed into an extracellular matrix/stromal vascular fraction gel. The standard processing procedure was established using quantized tests. The therapeutic potential of the product for wound healing was then tested. RESULTS Extracellular matrix/stromal vascular fraction gel derived from lipoaspirate and processed using a standard Coleman technique, followed by 1 minute of mechanical processing by passage back and forth between two 10-ml syringes at a flow rate of 10 ml/second, showed the highest adipose-derived stem cell and endothelial cell density. The stromal vascular fraction cells within the product also showed potential for multipotent differentiation similar to that of normal fat samples. In addition, the product showed better therapeutic results than stromal vascular fraction cell suspension when used to treat a nude mouse model of wound healing. CONCLUSIONS Extracellular matrix/stromal vascular fraction gel is an autologous injectable derived from native extracellular matrix and is a functional cellular component generated using a simple mechanical process. As such, it may offer a novel mode of tissue repair suitable for clinical application in stem cell therapies.
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