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Shiraishi M, Sowa Y, Sunaga A, Yamamoto K, Okazaki M. Bioengineering strategies for regeneration of skin integrity: A literature review. Regen Ther 2025; 28:153-160. [PMID: 39790492 PMCID: PMC11713503 DOI: 10.1016/j.reth.2024.12.006] [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: 08/18/2024] [Revised: 11/21/2024] [Accepted: 12/04/2024] [Indexed: 01/12/2025] Open
Abstract
Objective The skin is a complex organ that includes various stem cell populations. Current approaches for non-healing skin defects are sometimes inadequate and many attempts have been made to regenerate skin integrity. The aim of this review is to bridge the gap between basic research and clinical application of skin integrity regeneration. Methods A literature search was carried out in PubMed using combinations of the keywords "skin integrity", "tissue-engineered skin", "bioengineered skin", and "skin regeneration". Articles published from 1968 to 2023 reporting evidence from in vivo and in vitro skin regeneration experiments were included. Results These articles showed that stem cells can be differentiated into normal skin cells, including keratinocytes, and are a significant source of skin organoids, which are useful for investigating skin biology; and that emerging direct reprogramming methods have great potential to regenerate skin from the wounded skin surface. Conclusion Recent advances in skin regeneration will facilitate further advancement of both basic and clinical research in skin biology.
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Affiliation(s)
- Makoto Shiraishi
- Department of Plastic and Reconstructive Surgery, The University of Tokyo Hospital, Tokyo, Japan
| | - Yoshihiro Sowa
- Department of Plastic Surgery, Jichi Medical University, Japan
| | - Ataru Sunaga
- Department of Plastic Surgery, Jichi Medical University, Japan
| | - Kenta Yamamoto
- Department of Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Mutsumi Okazaki
- Department of Plastic and Reconstructive Surgery, The University of Tokyo Hospital, Tokyo, Japan
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Lee TL, Shen WC, Chen YC, Lai TC, Lin SR, Lin SW, Yu IS, Yeh YH, Li TK, Lee IT, Lee CW, Chen YL. Mir221- and Mir222-enriched adsc-exosomes mitigate PM exposure-exacerbated cardiac ischemia-reperfusion injury through the modulation of the BNIP3-MAP1LC3B-BBC3/PUMA pathway. Autophagy 2025; 21:374-393. [PMID: 39245438 PMCID: PMC11760231 DOI: 10.1080/15548627.2024.2395799] [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: 01/16/2024] [Revised: 08/19/2024] [Accepted: 08/20/2024] [Indexed: 09/10/2024] Open
Abstract
Epidemiology has shown a strong relationship between fine particulate matter (PM) exposure and cardiovascular disease. However, it remains unknown whether PM aggravates myocardial ischemia-reperfusion (I/R) injury, and the related mechanisms are unclear. Our previous study has shown that adipose stem cell-derived exosomes (ADSC-Exos) contain high levels of Mir221 and Mir222. The present study investigated the effects of PM exposure on I/R-induced cardiac injury through mitophagy and apoptosis, as well as the potential role of Mir221 and Mir222 in ADSC-Exos. Wild-type, mir221- and mir222-knockout (KO), and Mir221- and Mir222-overexpressing transgenic (TG) mice were intratracheally injected with PM (10 mg/kg). After 24 h, mice underwent left coronary artery ligation for 30 min, followed by 3 h of reperfusion (I/R). H9c2 cardiomyocytes were cultured under 1% O2 for 6 h, then reoxygenated for 12 h (hypoxia-reoxygenation [H/R]). PM aggravated I/R (or H/R) cardiac injury by increasing ROS levels and causing mitochondrial dysfunction, which increased the expression of mitochondrial fission-related proteins (DNM1L/Drp1 and MFF) and mitophagy-related proteins (BNIP3 and MAP1LC3B/LC3B) in vivo and in vitro. Treatment with ADSC-Exos or Mir221- and Mir222-mimics significantly reduced PM+I/R-induced cardiac injury. Importantly, ADSC-Exos contain Mir221 and Mir222, which directly targets BNIP3, MAP1LC3B/LC3B, and BBC3/PUMA, decreasing their expression and ultimately reducing cardiomyocyte mitophagy and apoptosis. The present data showed that ADSC-Exos treatment regulated mitophagy and apoptosis through the Mir221 and Mir222-BNIP3-MAP1LC3B-BBC3/PUMA pathway and significantly reduced the cardiac damage caused by PM+I/R. The present study revealed the novel therapeutic potential of ADSC-Exos in alleviating PM-induced exacerbation of myocardial I/R injury.Abbreviation: ADSC-Exos: adipose-derived stem cell exosomes; AL: autolysosome; ATP: adenosine triphosphate; BBC3/PUMA: BCL2 binding component 3; BNIP3: BCL2/adenovirus E1B interacting protein 3; CASP3: caspase 3; CASP9: caspase 9; CDKN1B/p27: cyclin dependent kinase inhibitor 1B; CVD: cardiovascular disease; DCFH-DA: 2',7'-dichlorodihydrofluorescein diacetate; DHE: dihydroethidium; DNM1L/Drp1: dynamin 1-like; EF: ejection fraction; FS: fractional shortening; H/R: hypoxia-reoxygenation; I/R: ischemia-reperfusion; LDH: lactate dehydrogenase; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; MFF: mitochondrial fission factor; miRNA: microRNA; NAC: N-acetylcysteine; OCR: oxygen consumption rate; PIK3C3/Vps34: phosphatidylinositol 3-kinase catalytic subunit type 3; PM: particulate matter; PRKAA1/AMPK: protein kinase AMP-activated catalytic subunit alpha 1; ROS: reactive oxygen species; SQSTM1/p62: sequestosome 1; TEM: transmission electron microscopy; TRP53/p53: transformation related protein 53; TUNEL: terminal deoxynucleotidyl transferase dUTP nick end labeling.
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Affiliation(s)
- Tzu-Lin Lee
- Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Wen-Chi Shen
- Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Ya-Chun Chen
- Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Tsai-Chun Lai
- Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan
- Department of Life Sciences, College of Life Sciences, National Chung Hsing University, Taichung, Taiwan
- The iEGG and Animal Biotechnology Center, National Chung Hsing University, Taichung, Taiwan
| | - Shu-Rung Lin
- Department of Bioscience Technology, College of Science, Chung Yuan Christian University, Taoyuan, Taiwan
- Center for Nanotechnology, Chung Yuan Christian University, Taoyuan, Taiwan
| | - Shu-Wha Lin
- Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - I-Shing Yu
- Laboratory Animal Center, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Yen-Hsiu Yeh
- Department and Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Tsai-Kun Li
- Department and Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan
- Center for Biotechnology, National Taiwan University, Taipei, Taiwan
- Centers for Genomic and Precision Medicine, National Taiwan University, Taipei, Taiwan
| | - I-Ta Lee
- School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan
| | - Chiang-Wen Lee
- Department of Orthopaedic Surgery, Chang Gung Memorial Hospital, Puzi, Chiayi, Taiwan
- Department of Nursing, Division of Basic Medical Sciences, and Chronic Diseases and Health Promotion Research Center Chang Gung University of Science and Technology, Puzi, Chiayi, Taiwan
- Research Center for Industry of Human Ecology and Research Center for Chinese Herbal Medicine, Chang Gung University of Science and Technology, Taoyuan, Taiwan
| | - Yuh-Lien Chen
- Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan
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Sajjad MW, Muzamil F, Sabir M, Ashfaq UA. Regenerative Medicine and Nanotechnology Approaches against Cardiovascular Diseases: Recent Advances and Future Prospective. Curr Stem Cell Res Ther 2025; 20:50-71. [PMID: 38343052 DOI: 10.2174/011574888x263530230921074827] [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: 05/22/2023] [Revised: 07/07/2023] [Accepted: 07/14/2023] [Indexed: 01/31/2025]
Abstract
Regenerative medicine refers to medical research focusing on repairing, replacing, or regenerating damaged or diseased tissues or organs. Cardiovascular disease (CVDs) is a significant health issue globally and is the leading cause of death in many countries. According to the Centers for Disease Control and Prevention (CDC), one person dies every 34 seconds in the United States from cardiovascular diseases, and according to a World Health Organization (WHO) report, cardiovascular diseases are the leading cause of death globally, taking an estimated 17.9 million lives each year. Many conventional treatments are available using different drugs for cardiovascular diseases, but these treatments are inadequate. Stem cells and nanotechnology are promising research areas for regenerative medicine treating CVDs. Regenerative medicines are a revolutionary strategy for advancing and successfully treating various diseases, intending to control cardiovascular disorders. This review is a comprehensive study of different treatment methods for cardiovascular diseases using different types of biomaterials as regenerative medicines, the importance of different stem cells in therapeutics, the expanded role of nanotechnology in treatment, the administration of several types of stem cells, their tracking, imaging, and the final observation of clinical trials on many different levels as well as it aims to keep readers up to pace on emerging therapeutic applications of some specific organs and disorders that may improve from regenerative medicine shortly.
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Affiliation(s)
- Muhammad Waseem Sajjad
- Department of Bioinformatics and Biotechnology, Government College University, Faisalabad, Pakistan
| | - Fatima Muzamil
- Department of Bioinformatics and Biotechnology, Government College University, Faisalabad, Pakistan
| | - Maida Sabir
- Department of Bioinformatics and Biotechnology, Government College University, Faisalabad, Pakistan
| | - Usman Ali Ashfaq
- Department of Bioinformatics and Biotechnology, Government College University, Faisalabad, Pakistan
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Razavi ZS, Farokhi S, Mahmoudvand G, Karimi-Rouzbahani A, Farasati-Far B, Tahmasebi-Ghorabi S, Pazoki-Toroudi H, Saadat-Fakhr M, Afkhami H. Stem cells and bio scaffolds for the treatment of cardiovascular diseases: new insights. Front Cell Dev Biol 2024; 12:1472103. [PMID: 39726717 PMCID: PMC11669526 DOI: 10.3389/fcell.2024.1472103] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2024] [Accepted: 10/01/2024] [Indexed: 12/28/2024] Open
Abstract
Mortality and morbidity from cardiovascular diseases are common worldwide. In order to improve survival and quality of life for this patient population, extensive efforts are being made to establish effective therapeutic modalities. New treatment options are needed, it seems. In addition to treating cardiovascular diseases, cell therapy is one of the most promising medical platforms. One of the most effective therapeutic approaches in this area is stem cell therapy. In stem cell biology, multipotent stem cells and pluripotent stem cells are divided into two types. There is evidence that stem cell therapy could be used as a therapeutic approach for cardiovascular diseases based on multiple lines of evidence. The effectiveness of stem cell therapies in humans has been studied in several clinical trials. In spite of the challenges associated with stem cell therapy, it appears that resolving them may lead to stem cells being used in cardiovascular disease patients. This may be an effective therapeutic approach. By mounting these stem cells on biological scaffolds, their effect can be enhanced.
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Affiliation(s)
- Zahra Sadat Razavi
- Physiology Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Simin Farokhi
- Student Research Committee, USERN Office, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Golnaz Mahmoudvand
- Student Research Committee, USERN Office, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Arian Karimi-Rouzbahani
- Student Research Committee, USERN Office, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Bahareh Farasati-Far
- Department of Chemistry, Iran University of Science and Technology, Tehran, Iran
| | - Samaneh Tahmasebi-Ghorabi
- Master of Health Education, Research Expert, Clinical Research Development Unit, Emam Khomeini Hospital, Ilam University of Medical Sciences, Ilam, Iran
| | | | - Masoud Saadat-Fakhr
- Faculty of Medicine, Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran
| | - Hamed Afkhami
- Cellular and Molecular Research Center, Qom University of Medical Sciences, Qom, Iran
- Nervous System Stem Cells Research Center, Semnan University of Medical Sciences, Semnan, Iran
- Department of Medical Microbiology, Faculty of Medicine, Shahed University, Tehran, Iran
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Suryawan IGR, Andrianto, Agita A, Ratri AK, Nugraha RA. Emerging therapeutic benefit of platelet-rich fibrin as novel platelet concentrates in tissue engineering. Glob Cardiol Sci Pract 2024; 2024:e202446. [PMID: 39931451 PMCID: PMC11807427 DOI: 10.21542/gcsp.2024.46] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2024] [Accepted: 10/15/2024] [Indexed: 02/13/2025] Open
Abstract
Background: Treating irreversible cardiomyocyte loss following myocardial infarction presents several therapeutic challenges. While cell therapy shows promise as a regenerative treatment for infarcted cardiac tissue, different cell sources vary in their therapeutic potential. Adipose-derived stem cells (ADSCs) have emerged as an attractive option due to their accessibility, but their limited differentiation capacity remains a significant constraint. Recent evidence suggests that injectable platelet-rich fibrin may enhance this process by stimulating the differentiation of ADSCs into cardiomyocyte-like cells. Objective: Analyse the benefit of injectable platelet-rich fibrin to accelerate the differentiation of adipose-derived mesenchymal stem cells into cardiomyocyte-like cells. Methods: This study is a true experimental randomized pos t-test design study. Adipose-derived mesenchymal stem cells were isolated from adipose tissue and expanded in culture through four passages. The characteristics of adipose-derived mesenchymal stem cells were measured by the expression of CD 34-, CD 45-, and CD 105+ using flowcytometry. The samples were divided into 3 groups, i.e., negative control (α-MEM), positive control (differentiation medium) and treatment group (platelet-rich fibrin). The assessment of GATA-4 marker expression was conducted using flowcytometry on the fifth day and troponin was conducted using immunocytochemistry on the tenth day to determine the differentiation to cardiomyocyte. Statistical analysis was performed using Student's t-tests and one-way ANOVA for data that demonstrated normal distribution as verified by the Shapiro-Wilk test. Results: Flowcytometry on GATA-4 expression revealed significant difference on addition of platelet-rich fibrin compared with negative and positive controls (68.20 ± 6.82 vs 58.15 ± 1.23; p < 0.05; 68.20 ± 6.82 vs 52.96 ± 2.02; p < 0.05). This was supported by the results of immunocytochemistry on troponin expression which revealed significant difference between platelet-rich fibrin group compared with negative and positive controls (50.66 ± 7.2 vs 10.73 ± 2.39; p < 0.05; 50.66 ± 7.2 vs 26.00 ± 0.4; p < 0.05). Conclusion: Injectable platelet-rich fibrin accelerates differentiation of adipose-derived mesenchymal stem cells into cardiomyocyte-like cells.
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Affiliation(s)
- I Gde Rurus Suryawan
- Division of Interventional Cardiology, Department of Cardiology and Vascular Medicine, Faculty of Medicine Universitas Airlangga - Dr. Soetomo Academic General Hospital
| | - Andrianto
- Division of Intensive and Acute Cardiovascular Care, Department of Cardiology and Vascular Medicine, Faculty of Medicine Universitas Airlangga. - Dr. Soetomo Academic General Hospital
| | - Arisya Agita
- Department of Cardiology, Mitra Keluarga Kenjeran, Surabaya
| | - Anudya Kartika Ratri
- Division of Pediatric Cardiology, Department of Cardiology and Vascular Medicine, Faculty of Medicine Universitas Airlangga - Dr. Soetomo Academic General Hospital
| | - Ricardo Adrian Nugraha
- Department of Cardiology and Vascular Medicine, Faculty of Medicine Universitas Airlangga - Dr. Soetomo Academic General Hospital
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Giugni FR, Giugni MDOV, Pinesi HT, Habrum FC, Laranjeira LN, Sady ERR, Suzumura EA, Gowdak LHW, Krieger JE. Safety and Efficacy of Adipose-Derived Mesenchymal Stem Cell Therapy for Ischemic Heart Disease: A Systematic Review. Arq Bras Cardiol 2024; 121:e20230830. [PMID: 39292063 PMCID: PMC11495568 DOI: 10.36660/abc.20230830] [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: 12/12/2023] [Revised: 05/02/2024] [Accepted: 06/12/2024] [Indexed: 09/19/2024] Open
Abstract
BACKGROUND Cell therapy using adipose-derived mesenchymal stem cells (ADSCs) shows great potential as a treatment for cardiovascular diseases. OBJECTIVE We conducted a systematic review to describe the safety and efficacy of ADSCs in ischemic heart disease. METHODS We searched PubMed/MEDLINE, EMBASE, Web of Science, CENTRAL, and LILACS (from inception to March 2024) for clinical studies involving ADSCs in patients with ischemic heart disease. We excluded studies involving patients with other types of heart disease, studies using mesenchymal stem cells derived from other tissues, as well as ongoing studies. Two independent reviewers screened the retrieved citations, extracted relevant data, and assessed the risk of bias in the included trials, using the Cochrane Collaboration criteria modified by McMaster University and Methodological Index for Non-Randomized Studies (MINORS). We used a narrative synthesis to present the results. RESULTS Ten studies (comprising 29 publications) met our inclusion criteria, including 8 randomized controlled trials and 2 uncontrolled trials. No severe adverse events associated with ADSC therapy were reported. While most efficacy endpoints did not reach statistical significance, there were reports of improved ischemic area, functional capacity, symptoms, and contractility in patients treated with ADSCs. CONCLUSIONS The findings from our review suggest that ADSC therapy is generally safe for patients with ischemic heart disease. However, further investigation is warranted to confirm its efficacy, particularly with larger clinical trials and in specific conditions where improvements in microcirculation may have a notable impact on clinical outcomes.
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Affiliation(s)
- Fernando Rabioglio Giugni
- The University of Texas Southwestern Medical CenterDallasTexasEUAThe University of Texas Southwestern Medical Center, Dallas, Texas – EUA
- Hospital das ClinicasFaculdade de MedicinaUniversidade de São PauloSão PauloSPBrasilInstituto do Coração InCor, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP – Brasil
| | - Melina de Oliveira Valdo Giugni
- Hospital das ClinicasFaculdade de MedicinaUniversidade de São PauloSão PauloSPBrasilInstituto do Coração InCor, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP – Brasil
- Baylor University Medical Center at DallasDallasTexasEUABaylor University Medical Center at Dallas, Dallas, Texas – EUA
| | - Henrique Trombini Pinesi
- Hospital das ClinicasFaculdade de MedicinaUniversidade de São PauloSão PauloSPBrasilInstituto do Coração InCor, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP – Brasil
| | - Fabio Cetinic Habrum
- Hospital das ClinicasFaculdade de MedicinaUniversidade de São PauloSão PauloSPBrasilInstituto do Coração InCor, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP – Brasil
| | - Lígia Nasi Laranjeira
- Hospital do CoraçãoSão PauloSPBrasilHospital do Coração (HCor), São Paulo, SP – Brasil
| | | | - Erica Aranha Suzumura
- Departmento de Medicina PreventivaFaculdade de MedicinaUniversidade de São PauloSão PauloSPBrasilDepartmento de Medicina Preventiva, Faculdade de Medicina FMUSP, Universidade de São Paulo, São Paulo, SP – Brasil
| | - Luis Henrique Wolff Gowdak
- Hospital das ClinicasFaculdade de MedicinaUniversidade de São PauloSão PauloSPBrasilInstituto do Coração InCor, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP – Brasil
| | - José Eduardo Krieger
- Hospital das ClinicasFaculdade de MedicinaUniversidade de São PauloSão PauloSPBrasilInstituto do Coração InCor, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP – Brasil
- Hospital do CoraçãoSão PauloSPBrasilHospital do Coração (HCor), São Paulo, SP – Brasil
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Zhang J, Li J, Qu X, Liu Y, Sun L, Harada A, Hua Y, Sougawa N, Tabata A, Liu L, Miyagawa S. Development of composite functional tissue sheets using hiPSC-CMs and hADSCs to improve the cardiac function after myocardial infarction. Bioact Mater 2024; 37:533-548. [PMID: 38689657 PMCID: PMC11058078 DOI: 10.1016/j.bioactmat.2024.03.028] [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: 01/09/2024] [Revised: 02/28/2024] [Accepted: 03/21/2024] [Indexed: 05/02/2024] Open
Abstract
Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been widely used in therapy of ischemic heart disease. However, there are still remaining issues that limit the therapeutic efficacy, such as immune rejection and low retention of hiPSC-CMs. Human adipose mesenchymal stromal cells (hADSCs) have been reported to be able to regulate the immune response, promote angiogenesis and promote the maturation of hiPSC-CMs. In this study, we co-cultured these two types of cells on fiber scaffold made of biodegradable poly (D,L-lactic-co-glycolic acid) (PLGA) polymer for several days to develop a composited 3D cardiac tissue sheet. As expected, the cells formed 231.00 ± 15.14 μm thickness tissue, with improved organization, alignment, ECM condition, contractile ability, and paracrine function compared to culture hiPSC-CMs only on PLGA fiber. Furthermore, the composited 3D cardiac tissue sheet significantly promoted the engraftment and survival after transplantation. The composited 3D cardiac tissue sheet also increased cardiac function, attenuated ventricular remodeling, decreased fibrosis, and enhanced angiogenesis in rat myocardial infarction model, indicating that this strategy wound be a promising therapeutic option in the clinical scenario.
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Affiliation(s)
- Jingbo Zhang
- Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Osaka, 565-0871, Japan
| | - Junjun Li
- Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Osaka, 565-0871, Japan
- Department of Applied Physics Osaka University, Osaka University, 2-2 Yamada-oka, Osaka, 565-0871, Japan
| | - Xiang Qu
- Frontier of Regenerative Medicine, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka, 565-0871, Japan
| | - Yuting Liu
- Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Osaka, 565-0871, Japan
| | - Lifu Sun
- Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Osaka, 565-0871, Japan
| | - Akima Harada
- Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Osaka, 565-0871, Japan
| | - Ying Hua
- Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Osaka, 565-0871, Japan
| | - Nagako Sougawa
- Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Osaka, 565-0871, Japan
- Department of Physiology, Osaka Dental University, 8-1 Kuzuha Hanazono-cho, Hirakata, 573-1121, Japan
| | - Akiko Tabata
- Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Osaka, 565-0871, Japan
| | - Li Liu
- Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Osaka, 565-0871, Japan
- Department of Applied Physics Osaka University, Osaka University, 2-2 Yamada-oka, Osaka, 565-0871, Japan
| | - Shigeru Miyagawa
- Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Osaka, 565-0871, Japan
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Meechem MB, Jadli AS, Patel VB. Uncovering the link between diabetes and cardiovascular diseases: insights from adipose-derived stem cells. Can J Physiol Pharmacol 2024; 102:229-241. [PMID: 38198660 DOI: 10.1139/cjpp-2023-0282] [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] [Indexed: 01/12/2024]
Abstract
Cardiovascular diseases (CVDs) are the leading causes of morbidity and mortality worldwide. The escalating global occurrence of obesity and diabetes mellitus (DM) has led to a significant upsurge in individuals afflicted with CVDs. As the prevalence of CVDs continues to rise, it is becoming increasingly important to identify the underlying cellular and molecular mechanisms that contribute to their development and progression, which will help discover novel therapeutic avenues. Adipose tissue (AT) is a connective tissue that plays a crucial role in maintaining lipid and glucose homeostasis. However, when AT is exposed to diseased conditions, such as DM, this tissue will alter its phenotype to become dysfunctional. AT is now recognized as a critical contributor to CVDs, especially in patients with DM. AT is comprised of a heterogeneous cellular population, which includes adipose-derived stem cells (ADSCs). ADSCs resident in AT are believed to regulate physiological cardiac function and have potential cardioprotective roles. However, recent studies have also shown that ADSCs from various adipose tissue depots become pro-apoptotic, pro-inflammatory, less angiogenic, and lose their ability to differentiate into various cell lineages upon exposure to diabetic conditions. This review aims to summarize the current understanding of the physiological roles of ADSCs, the impact of DM on ADSC phenotypic changes, and how these alterations may contribute to the pathogenesis of CVDs.
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Affiliation(s)
- Megan B Meechem
- Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Libin Cardiovascular Institute, University of Calgary, Calgary, AB, Canada
| | - Anshul S Jadli
- Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Libin Cardiovascular Institute, University of Calgary, Calgary, AB, Canada
| | - Vaibhav B Patel
- Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Libin Cardiovascular Institute, University of Calgary, Calgary, AB, Canada
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Tsai IT, Sun CK. Stem Cell Therapy against Ischemic Heart Disease. Int J Mol Sci 2024; 25:3778. [PMID: 38612587 PMCID: PMC11011361 DOI: 10.3390/ijms25073778] [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: 02/07/2024] [Revised: 03/12/2024] [Accepted: 03/26/2024] [Indexed: 04/14/2024] Open
Abstract
Ischemic heart disease, which is one of the top killers worldwide, encompasses a series of heart problems stemming from a compromised coronary blood supply to the myocardium. The severity of the disease ranges from an unstable manifestation of ischemic symptoms, such as unstable angina, to myocardial death, that is, the immediate life-threatening condition of myocardial infarction. Even though patients may survive myocardial infarction, the resulting ischemia-reperfusion injury triggers a cascade of inflammatory reactions and oxidative stress that poses a significant threat to myocardial function following successful revascularization. Moreover, despite evidence suggesting the presence of cardiac stem cells, the fact that cardiomyocytes are terminally differentiated and cannot significantly regenerate after injury accounts for the subsequent progression to ischemic cardiomyopathy and ischemic heart failure, despite the current advancements in cardiac medicine. In the last two decades, researchers have realized the possibility of utilizing stem cell plasticity for therapeutic purposes. Indeed, stem cells of different origin, such as bone-marrow- and adipose-derived mesenchymal stem cells, circulation-derived progenitor cells, and induced pluripotent stem cells, have all been shown to play therapeutic roles in ischemic heart disease. In addition, the discovery of stem-cell-associated paracrine effects has triggered intense investigations into the actions of exosomes. Notwithstanding the seemingly promising outcomes from both experimental and clinical studies regarding the therapeutic use of stem cells against ischemic heart disease, positive results from fraud or false data interpretation need to be taken into consideration. The current review is aimed at overviewing the therapeutic application of stem cells in different categories of ischemic heart disease, including relevant experimental and clinical outcomes, as well as the proposed mechanisms underpinning such observations.
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Affiliation(s)
- I-Ting Tsai
- Department of Emergency Medicine, E-Da Hospital, I-Shou University, Kaohsiung City 82445, Taiwan;
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung City 82445, Taiwan
| | - Cheuk-Kwan Sun
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung City 82445, Taiwan
- Department of Emergency Medicine, E-Da Dachang Hospital, I-Shou University, Kaohsiung City 80794, Taiwan
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Luo ZR, Meng WT, Li H, Wang Y, Wang YC, Zhao Y, Lu PP, Yuan Y, Huang W, Guo HD. Transplantation of induced pluripotent stem cells-derived cardiomyocytes combined with modified Taohong Siwu decoction improved heart repair after myocardial infarction. Heliyon 2024; 10:e26700. [PMID: 38434034 PMCID: PMC10906439 DOI: 10.1016/j.heliyon.2024.e26700] [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: 10/29/2022] [Revised: 02/02/2024] [Accepted: 02/19/2024] [Indexed: 03/05/2024] Open
Abstract
Objective This study aimed to study whether modified Taohong Siwu decoction (MTHSWD) combined with human induced pluripotent stem cells-derived cardiomyocytes (iPS-CMs) transplantation can promote cardiac function in myocardial infarction (MI) nude mouse model and explore its possible mechanism. Methods The MI mouse model was established by the ligation of left anterior descending coronary artery. After 4 weeks of gavage of MTHSWD combined with iPS-CMs transplantation, the changes in heart function of mice were examined by echocardiography. The histological changes were observed by Masson's trichrome staining. The survival and differentiation of transplanted cells were detected by double immunofluorescence staining of human nuclear antigen (HNA) and cardiac troponin T (cTnT). The number of c-kit-positive cells in the infarct area were evaluated by immunofluorescent staining. The levels of stromal cell-derived factor 1 (SDF-1), stem cell factor (SCF), vascular endothelial growth factor (VEGF) and basic fibroblast growth factor in infarcted myocardium tissues were detected by ELISA. Results MTHSWD combined with iPS-CMs transplantation can improve the heart function of MI mice, reduce the infarct size and collagen deposition in infarct area. By immunofluorescence double-label detection of HNA and cTnT, it was found that MTHSWD combined with iPS-CMs transplantation can improve the survival and maturation of iPS-CMs. In addition, MTHSWD combined with iPS-CMs transplantation can activate more endogenous c-kit positive cardiac mesenchymal cells, and significantly increase the content of SDF-1, SCF and VEGF in myocardial tissues. Conclusions The combination of MTHSWD with iPS-CMs transplantation promoted cardiac function of nude mice with MI by improving the survival and maturation of iPS-CMs in the infarct area, activating the endogenous c-kit positive cardiac mesenchymal cells, and increasing paracrine.
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Affiliation(s)
- Zhi-rong Luo
- Academy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
- Department of Anatomy, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Wan-ting Meng
- Academy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
- Department of Anatomy, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Han Li
- Academy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
- Department of Anatomy, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Yu Wang
- Academy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Ya-chao Wang
- Academy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
- Department of Anatomy, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Yue Zhao
- Academy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
- Department of Anatomy, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Ping-ping Lu
- Department of Anatomy, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Yuan Yuan
- Academy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Wei Huang
- Department of Chinese Internal Medicine, Dahua Hospital, Xuhui District, Shanghai, China
| | - Hai-dong Guo
- Academy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
- Department of Anatomy, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
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11
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Karna S, Kang KW. An Overview of the Mechanism behind Excessive Volume of Pericardial Fat in Heart Failure. J Obes Metab Syndr 2023; 32:322-329. [PMID: 38036419 PMCID: PMC10786210 DOI: 10.7570/jomes23042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2023] [Revised: 09/11/2023] [Accepted: 10/11/2023] [Indexed: 12/02/2023] Open
Abstract
Heart failure (HF) is a clinical syndrome characterized by myocardial dysfunction leading to inefficient blood filling or ejection. Regardless of the etiology, various mechanisms, including adipokine hypersecretion, proinflammatory cytokines, stem cell proliferation, oxidative stress, hyperglycemic toxicity, and autonomic nervous system dysregulation in the pericardial fat (PCF), contribute to the development of HF. PCF has been directly associated with cardiovascular disease, and an increased PCF volume is associated with HF. The PCF acts as neuroendocrine tissue that is closely linked to myocardial function and acts as an energy reservoir. This review aims to summarize each mechanism associated with PCF in HF.
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Affiliation(s)
- Sandeep Karna
- Division of Cardiology, Cardiovascular Arrhythmia Center, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Korea
| | - Ki-Woon Kang
- Division of Cardiology, Cardiovascular Arrhythmia Center, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Korea
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12
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Olejarz W, Sadowski K, Radoszkiewicz K. Extracellular Vesicles in Atherosclerosis: State of the Art. Int J Mol Sci 2023; 25:388. [PMID: 38203558 PMCID: PMC10779125 DOI: 10.3390/ijms25010388] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Revised: 12/17/2023] [Accepted: 12/25/2023] [Indexed: 01/12/2024] Open
Abstract
Atherosclerosis is a chronic inflammatory disease driven by lipid accumulation in the arteries, leading to narrowing and thrombosis that causes mortality. Emerging evidence has confirmed that atherosclerosis affects younger people and is involved in the majority of deaths worldwide. EVs are associated with critical steps in atherosclerosis, cholesterol metabolism, immune response, endothelial dysfunction, vascular inflammation, and remodeling. Endothelial cell-derived EVs can interact with platelets and monocytes, thereby influencing endothelial dysfunction, atherosclerotic plaque destabilization, and the formation of thrombus. EVs are potential diagnostic and prognostic biomarkers in atherosclerosis (AS) and cardiovascular disease (CVD). Importantly, EVs derived from stem/progenitor cells are essential mediators of cardiogenesis and cardioprotection and may be used in regenerative medicine and tissue engineering.
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Affiliation(s)
- Wioletta Olejarz
- Department of Biochemistry and Pharmacogenomics, Faculty of Pharmacy, Medical University of Warsaw, 02-091 Warsaw, Poland;
- Centre for Preclinical Research, Medical University of Warsaw, 02-091 Warsaw, Poland
| | - Karol Sadowski
- Department of Biochemistry and Pharmacogenomics, Faculty of Pharmacy, Medical University of Warsaw, 02-091 Warsaw, Poland;
- Centre for Preclinical Research, Medical University of Warsaw, 02-091 Warsaw, Poland
| | - Klaudia Radoszkiewicz
- Translational Platform for Regenerative Medicine, Mossakowski Medical Research Institute, Polish Academy of Sciences, 02-106 Warsaw, Poland;
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13
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Zhang J, Li J, Qu X, Liu Y, Harada A, Hua Y, Yoshida N, Ishida M, Tabata A, Sun L, Liu L, Miyagawa S. Development of a thick and functional human adipose-derived stem cell tissue sheet for myocardial infarction repair in rat hearts. Stem Cell Res Ther 2023; 14:380. [PMID: 38124195 PMCID: PMC10734106 DOI: 10.1186/s13287-023-03560-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2023] [Accepted: 11/03/2023] [Indexed: 12/23/2023] Open
Abstract
BACKGROUND Heart failure (HF) is a major cause of death worldwide. The most effective treatment for HF is heart transplantation, but its use is limited by the scarcity of donor hearts. Recently, stem cell-based therapy has emerged as a promising approach for treating myocardial infarction. Our research group has been investigating the use of human induced pluripotent stem cell-derived cardiomyocyte patches as a potential therapeutic candidate. We have successfully conducted eight cases of clinical trials and demonstrated the safety and effectiveness of this approach. However, further advancements are necessary to overcome immune rejection and enhance therapeutic efficacy. In this study, we propose a novel and efficient technique for constructing mesenchymal stem cell (MSC) tissue sheets, which can be transplanted effectively for treating myocardial infarction repair. METHODS We applied a one-step method to construct the human adipose-derived mesenchymal stem cell (hADSC) tissue sheet on a poly(lactic-co-glycolic acid) fiber scaffold. Histology, immunofluorescence, and paracrine profile assessment were used to determine the organization and function of the hADSC tissue sheet. Echocardiography and pathological analyses of heart sections were performed to evaluate cardiac function, fibrosis area, angiogenesis, and left ventricular remodeling. RESULTS In vitro, the hADSC tissue sheet showed great organization, abundant ECM expression, and increased paracrine secretion than single cells. In vivo, the hADSC tissue sheet group demonstrated improved cardiac functional recovery, less ventricular remodeling, decreased fibrosis, and enhanced angiogenesis than the MI group. CONCLUSIONS We developed thick and functional hADSC tissue sheets via the one-step strategy. The hADSC tissue sheet showed excellent performance in treating myocardial infarction in the rat model.
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Affiliation(s)
- Jingbo Zhang
- Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, 2-2 Yamada-Oka, Suita, Osaka, 565-0871, Japan
| | - Junjun Li
- Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, 2-2 Yamada-Oka, Suita, Osaka, 565-0871, Japan
- Frontier of Regenerative Medicine, Osaka University Graduate School of Medicine, 2-2 Yamada-Oka, Suita, Osaka, 565-0871, Japan
| | - Xiang Qu
- Frontier of Regenerative Medicine, Osaka University Graduate School of Medicine, 2-2 Yamada-Oka, Suita, Osaka, 565-0871, Japan
| | - Yuting Liu
- Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, 2-2 Yamada-Oka, Suita, Osaka, 565-0871, Japan
| | - Akima Harada
- Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, 2-2 Yamada-Oka, Suita, Osaka, 565-0871, Japan
| | - Ying Hua
- Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, 2-2 Yamada-Oka, Suita, Osaka, 565-0871, Japan
| | - Noriko Yoshida
- Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, 2-2 Yamada-Oka, Suita, Osaka, 565-0871, Japan
| | - Masako Ishida
- Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, 2-2 Yamada-Oka, Suita, Osaka, 565-0871, Japan
| | - Akiko Tabata
- Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, 2-2 Yamada-Oka, Suita, Osaka, 565-0871, Japan
| | - Lifu Sun
- Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, 2-2 Yamada-Oka, Suita, Osaka, 565-0871, Japan
| | - Li Liu
- Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, 2-2 Yamada-Oka, Suita, Osaka, 565-0871, Japan.
- Frontier of Regenerative Medicine, Osaka University Graduate School of Medicine, 2-2 Yamada-Oka, Suita, Osaka, 565-0871, Japan.
| | - Shigeru Miyagawa
- Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, 2-2 Yamada-Oka, Suita, Osaka, 565-0871, Japan.
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14
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Barik P, Kuo WW, Kuo CH, Hsieh DJY, Day CH, Daddam J, Chen MYC, Padma VV, Shibu MA, Huang CY. Rewiring of IGF1 secretion and enhanced IGF1R signaling induced by co-chaperone carboxyl-terminus of Hsp70 interacting protein in adipose-derived stem cells provide augmented cardioprotection in aging-hypertensive rats. Aging (Albany NY) 2023; 15:14019-14038. [PMID: 38085649 PMCID: PMC10756089 DOI: 10.18632/aging.205287] [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: 09/01/2021] [Accepted: 10/04/2023] [Indexed: 12/21/2023]
Abstract
Aging-associated cardiovascular diseases depend on the longitudinal deterioration of stem cell dynamics. The entire mechanism behind it is not completely understood. However, many studies suggest that endocrine pathways, particularly the insulin-like growth factor-1(IGF1) signaling pathway are involved in cardioprotection, especially in stem-cell treatments. Here, we investigated the role of a co-chaperone, carboxyl-terminus of Hsp70 interacting protein (CHIP) in the aspects of growth factor secretion and receptor stabilization in mesenchymal stem cells (MSCs). Briefly, we overexpressed CHIP in rat adipose-derived stem cells (rADSCs) and explored the consequences in vitro, and in vivo, in spontaneously hypertensive rats (SHR). Our data revealed that CHIP overexpression in rADSCs promoted the secretion of insulin-like growth factor-1 (IGF1) and IGF binding protein-3 (IGFBP3) as per immunoblot/cytokine array analysis. We also found that these results were dependent on the nuclear translocation of signal transducer and activator of transcription 3 (STAT3) in rADSCs. Further, the CHIP co-chaperone was also involved in the stabilization of the receptor of IGF1 (IGF1R); interactions between the beta transmembrane region of IGF1R, and the tetracopeptide repeat (TPR) domain of CHIP were evident. Importantly, after the transplantation of lentiviral CHIP overexpression of rADSCs (rADSCsCHIP-WT) into nine months aging-SHR led to an increase in their cardiac function - increased ejection fraction and fractional shortening (≈15% vs. control SHR) - as well as a decrease in their heart size and heart rate, respectively. Altogether, our results support the use of CHIP overexpressing stem cells for the mitigation of cardiac hypertrophy and remodeling associated with late-stage hypertension.
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Affiliation(s)
- Parthasarathi Barik
- Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan
| | - Wei-Wen Kuo
- Department of Biological Science and Technology, China Medical University, Taichung, Taiwan
| | - Chia-Hua Kuo
- Laboratory of Exercise Biochemistry, University of Taipei, Taipei, Taiwan
| | - Dennis Jine-Yuan Hsieh
- School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan
- Clinical Laboratory, Chung Shan Medical University Hospital, Taichung, Taiwan
| | | | - Jayasimharayalu Daddam
- Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
| | | | - V. Vijaya Padma
- Department of Biotechnology, Bharathiar University, Coimbatore, India
| | | | - Chih-Yang Huang
- Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan
- Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
- Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan
- Department of Biotechnology, Asia University, Taichung, Taiwan
- Center of General Education, Buddhist Tzu Chi Medical Foundation, Tzu Chi University of Science and Technology, Hualien, Taiwan
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15
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Piao J, Cho H, Park JH, Yoo KH, Jeong I, Hong HS. Preconditioning with Substance P Restores Therapeutic Efficacy of Aged ADSC by Elevating TNFR2 and Paracrine Potential. BIOLOGY 2023; 12:1458. [PMID: 38132284 PMCID: PMC10740808 DOI: 10.3390/biology12121458] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/11/2023] [Revised: 11/16/2023] [Accepted: 11/21/2023] [Indexed: 12/23/2023]
Abstract
Aging leads to a decline in stem cell activity by reducing the repopulation rate and paracrine potential, ultimately diminishing efficacy in vivo. TNF-α can exert inflammatory and cell death actions via Erk by binding to TNFR-1, and survival and tissue repair actions via Akt by binding to TNFR-2. Aged cells are reported to have insufficient expression of TNFR-2, indicating that aged adipose-derived stem cells (ADSCs-E) lack the ability for cell survival and immune control compared to young ADSCs (ADSCs-Y). This study aims to assess the preconditioning effect of SP on the response of ADSCs-E to inflammation. ADSCs-E were treated with SP and then exposed to a high dose of TNF-α for 24 h. Consequently, ADSC-E exhibited weaker viability and lower TNFR2 levels compared to ADSC-Y. In response to TNF-α, the difference in TNFR2 expression became more pronounced in ADSC-E and ADSC-Y. Moreover, ADSC-E showed a severe deficiency in proliferation and paracrine activity. However, preconditioning with SP significantly enhanced the viability of ADSCs-E and also restored TNFR2 expression and paracrine potential, similar to ADSC-Y under inflammatory conditions. Our findings support the idea that preconditioning with SP has the potential to restore the cellular function of senescent stem cells before transplantation.
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Affiliation(s)
- Jiyuan Piao
- Department of Genetic Engineering, Graduate School of Biotechnology, Kyung Hee University, Yongin-si 17104, Republic of Korea; (J.P.)
| | - Hyunchan Cho
- Department of Genetic Engineering, Graduate School of Biotechnology, Kyung Hee University, Yongin-si 17104, Republic of Korea; (J.P.)
| | - Jong Hyun Park
- Department of Dance, College of Performing Arts & Sport, Han Yang University, Seoul 04763, Republic of Korea
| | - Ki Hyun Yoo
- SIMPLE Planet Inc., Seoul 04790, Republic of Korea
| | - Ildoo Jeong
- SIMPLE Planet Inc., Seoul 04790, Republic of Korea
| | - Hyun Sook Hong
- Department of Biomedical Science and Technology, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea
- East-West Medical Research Institute, Kyung Hee University, Seoul 02447, Republic of Korea
- Kyung Hee Institute of Regenerative Medicine (KIRM), Medical Science Research Institute, Kyung Hee University Medical Center, Seoul 02447, Republic of Korea
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16
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El-Husseiny HM, Mady EA, Usui T, Ishihara Y, Yoshida T, Kobayashi M, Sasaki K, Ma D, Yairo A, Mandour AS, Hendawy H, Doghish AS, Mohammed OA, Takahashi K, Tanaka R. Adipose Stem Cell-Seeded Decellularized Porcine Pericardium: A Promising Functional Biomaterial to Synergistically Restore the Cardiac Functions Post-Myocardial Infarction. Vet Sci 2023; 10:660. [PMID: 37999483 PMCID: PMC10675230 DOI: 10.3390/vetsci10110660] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2023] [Revised: 10/19/2023] [Accepted: 11/15/2023] [Indexed: 11/25/2023] Open
Abstract
Myocardial infarction (MI) is a serious cardiovascular disease as the leading cause of death globally. Hence, reconstruction of the cardiac tissue comes at the forefront of strategies adopted to restore heart functions following MI. In this investigation, we studied the capacity of rat adipose-derived mesenchymal stem cells (r-AdMSCs) and decellularized porcine pericardium (DPP) to restore heart functions in MI animals. MI was induced in four different groups, three of which were treated either using DPP (MI-DPP group), stem cells (MI-SC group), or both (MI-SC/DPP group). Cardiac functions of these groups and the Sham group were evaluated using echocardiography, the intraventricular pressure gradient (IVPG) on weeks 2 and 4, and intraventricular hemodynamics on week 4. On day 31, the animals were euthanized for histological analysis. Echocardiographic, IVPG and hemodynamic findings indicated that the three treatment strategies shared effectively in the regeneration process. However, the MI-SC/DPP group had a unique synergistic ability to restore heart functions superior to the other treatment protocols. Histology showed that the MI-SC/DPP group presented the lowest (p < 0.05) degeneration score and fibrosis % compared to the other groups. Conclusively, stem cell-seeded DPP is a promising platform for the delivery of stem cells and restoration of heart functions post-MI.
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Affiliation(s)
- Hussein M. El-Husseiny
- Laboratory of Veterinary Surgery, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai Cho, Fuchu-shi 183-8509, Tokyo, Japan; (K.S.); (D.M.); (A.Y.); (A.S.M.); (H.H.)
- Department of Surgery, Anesthesiology, and Radiology, Faculty of Veterinary Medicine, Benha University, Moshtohor, Toukh 13736, Elqaliobiya, Egypt
| | - Eman A. Mady
- Laboratory of Veterinary Physiology, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai Cho, Fuchu-shi 183-8509, Tokyo, Japan;
- Department of Animal Hygiene, Behavior and Management, Faculty of Veterinary Medicine, Benha University, Moshtohor, Toukh 13736, Elqaliobiya, Egypt
| | - Tatsuya Usui
- Laboratory of Veterinary Pharmacology, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai Cho, Fuchu-shi 183-8509, Tokyo, Japan; (T.U.); (Y.I.)
| | - Yusuke Ishihara
- Laboratory of Veterinary Pharmacology, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai Cho, Fuchu-shi 183-8509, Tokyo, Japan; (T.U.); (Y.I.)
| | - Toshinori Yoshida
- Laboratory of Veterinary Pathology, Division of Animal Life Science, Institute of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi 183-8509, Tokyo, Japan; (T.Y.); (M.K.)
| | - Mio Kobayashi
- Laboratory of Veterinary Pathology, Division of Animal Life Science, Institute of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi 183-8509, Tokyo, Japan; (T.Y.); (M.K.)
| | - Kenta Sasaki
- Laboratory of Veterinary Surgery, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai Cho, Fuchu-shi 183-8509, Tokyo, Japan; (K.S.); (D.M.); (A.Y.); (A.S.M.); (H.H.)
| | - Danfu Ma
- Laboratory of Veterinary Surgery, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai Cho, Fuchu-shi 183-8509, Tokyo, Japan; (K.S.); (D.M.); (A.Y.); (A.S.M.); (H.H.)
- College of Veterinary Medicine, Nanjing Agricultural University, No. 1 Wei-Gang, Xuanwu District, Nanjing 210095, China
| | - Akira Yairo
- Laboratory of Veterinary Surgery, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai Cho, Fuchu-shi 183-8509, Tokyo, Japan; (K.S.); (D.M.); (A.Y.); (A.S.M.); (H.H.)
| | - Ahmed S. Mandour
- Laboratory of Veterinary Surgery, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai Cho, Fuchu-shi 183-8509, Tokyo, Japan; (K.S.); (D.M.); (A.Y.); (A.S.M.); (H.H.)
- Department of Animal Medicine (Internal Medicine), Faculty of Veterinary Medicine, Suez Canal University, Ismailia 41522, Ismailia, Egypt
| | - Hanan Hendawy
- Laboratory of Veterinary Surgery, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai Cho, Fuchu-shi 183-8509, Tokyo, Japan; (K.S.); (D.M.); (A.Y.); (A.S.M.); (H.H.)
- Department of Veterinary Surgery, Faculty of Veterinary Medicine, Suez Canal University, Ismailia 41522, Ismailia, Egypt
| | - Ahmed S. Doghish
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City 11829, Cairo, Egypt;
- Department of Biochemistry, and Molecular Biology Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11651, Cairo, Egypt
| | - Osama A. Mohammed
- Department of Clinical Pharmacology, College of Medicine, University of Bisha, Bisha 61922, Saudi Arabia;
| | - Ken Takahashi
- Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, Bunkyo 113-8421, Tokyo, Japan;
| | - Ryou Tanaka
- Laboratory of Veterinary Surgery, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai Cho, Fuchu-shi 183-8509, Tokyo, Japan; (K.S.); (D.M.); (A.Y.); (A.S.M.); (H.H.)
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17
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Mansano BSDM, da Rocha VP, Teixeira ILA, de Oliveira HA, Vieira SS, Antonio EL, Tucci PJF, Serra AJ. Light-emitting Diode Can Enhance the Metabolism and Paracrine Action of Mesenchymal Stem Cells. Photochem Photobiol 2023; 99:1420-1428. [PMID: 36807286 DOI: 10.1111/php.13794] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Accepted: 02/16/2023] [Indexed: 02/22/2023]
Abstract
This study investigated the influence of red light-emitting diodes (LED, 630 nm) on different irradiation parameters and the number of applications on mesenchymal stem cells derived from adipose tissue (AdMSCs) metabolism and paracrine factors. The AdMSCs were irradiated with a LEDbox device (output power: 2452.5 mW; laser beam: 163.5 cm2 ; irradiance: 15 mW cm-2 ) using radiant exposures of 0.5, 2, and 4 J cm-2 , respectively. AdMSCs were irradiated once or every 48 h up to three irradiations. All molecular analyses were performed 24 h after the last irradiation. LED did not induce changes in cell count, DNA damage, and oxidative stress. A significant repercussion of the LED has been noticed after three irradiations with 4 J cm-2 . AdMSCs had higher levels of IL-6, IGF-1, and NOx index. A higher ATP content and MMT/Resazurin assay were identified in AdMSCs irradiated three times with 4 J cm-2 . Mitochondrial basal respiration, maximal respiration and proton leak under metabolic stress were reduced by 0.5 and 2 J cm-2 irradiations. These data showed that three LED irradiations with 4 J cm-2 may be a suitable parameter for future AdMSCs therapy because of its improved metabolic activity, ATP content, and IL-6, IGF-1, and nitric oxide secretion.
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Affiliation(s)
| | - Vitor Pocani da Rocha
- Cardiology Division, Department of Medicine, Federal University of Sao Paulo, São Paulo, SP, Brazil
| | | | | | - Stella Souza Vieira
- Cardiology Division, Department of Medicine, Federal University of Sao Paulo, São Paulo, SP, Brazil
- Base Hospital Foundation, Medicine School of São José do Rio Preto, Sao Paulo, SP, Brazil
| | - Ednei Luiz Antonio
- Cardiology Division, Department of Medicine, Federal University of Sao Paulo, São Paulo, SP, Brazil
| | | | - Andrey Jorge Serra
- Cardiology Division, Department of Medicine, Federal University of Sao Paulo, São Paulo, SP, Brazil
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18
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Barbara Di Stefano A, Toia F, Urrata V, Trapani M, Montesano L, Cammarata E, Moschella F, Cordova A. Spheroids of adipose derived stem cells show their potential in differentiating towards the angiogenic lineage. Gene 2023:147578. [PMID: 37336277 DOI: 10.1016/j.gene.2023.147578] [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: 01/10/2023] [Revised: 05/29/2023] [Accepted: 06/14/2023] [Indexed: 06/21/2023]
Abstract
INTRODUCTION Adipose derived stem cells (ASCs) are a mesenchymal stem cell population of great scientific interest due to their abundance and easiness in obtaining them from adipose tissue. Recently, several techniques for three dimensional (3D) ASCs cultivation have been developed to obtain spheroids of adipose stem cells (SASCs). It was already proved that ASCs are able to differentiate towards the endothelial lineage thus, for the first time, we investigated the ability of our 3D SASCs to differentiate endothelially and the effects of not differentiated SASC secreted factors on specific cultured cells. MATERIALS AND METHODS SASCs were differentiated with a specific medium towards endothelial lineage. Cell viability, gene and protein expression of typical endothelial markers were analysed. Moreover, tube formation, wound healing and migration assays were performed to investigate the ability in migration and angiogenic networks formation of endothelially differentiated cells. SASCs secretome were also tested. RESULTS We showed the ability of SASCs to differentiate towards the endothelial lineage with an increase in cell viability of 15-fold and 8-fold at 14 and 21 days of differentiation respectively. Moreover, we showed the upregulation of VEGF-A and CD31 mRNAs of 9-fold and 1300-fold in SASCs endothelially differentiated cells, whilst protein expression was different. VEGF-A protein expression was upregulated whilst CD31 protein wasn't translated. In addition, ICAM1, VCAM1, ANGPT1, CD62E protein levels remain unchanged. SASCs were also able to organize themselves into angiogenic networks after 7 days of culturing themon ECMatrix. Secreted factors from undifferentiated 3D SASCs acted in a paracrine way on HUVECs and endothelially differentiated ASCs seeded on ECMatrix to promote angiogenic events. CONCLUSIONS SASCs, thanks to their multilineage differentiation potential, also possess the ability to differentiate towards endothelial lineage and to organize themselves into angiogenic networks. Moreover, they are able to promote angiogenesis through their secreted factors.
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Affiliation(s)
- Anna Barbara Di Stefano
- BIOPLAST-Laboratory of BIOlogy and Regenerative Medicine-PLASTic Surgery, Plastic and Reconstructive Surgery Section, Department of Surgical, Oncological and Oral Sciences, University of Palermo, 90127 Palermo, Italy.
| | - Francesca Toia
- BIOPLAST-Laboratory of BIOlogy and Regenerative Medicine-PLASTic Surgery, Plastic and Reconstructive Surgery Section, Department of Surgical, Oncological and Oral Sciences, University of Palermo, 90127 Palermo, Italy; Section of Plastic and Reconstructive Surgery. Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy; Plastic and Reconstructive Unit, Department of D.A.I. Chirurgico, Azienda Ospedaliera Universitaria Policlinico "Paolo Giaccone", 90127, Palermo, Italy
| | - Valentina Urrata
- BIOPLAST-Laboratory of BIOlogy and Regenerative Medicine-PLASTic Surgery, Plastic and Reconstructive Surgery Section, Department of Surgical, Oncological and Oral Sciences, University of Palermo, 90127 Palermo, Italy
| | - Marco Trapani
- BIOPLAST-Laboratory of BIOlogy and Regenerative Medicine-PLASTic Surgery, Plastic and Reconstructive Surgery Section, Department of Surgical, Oncological and Oral Sciences, University of Palermo, 90127 Palermo, Italy
| | - Luigi Montesano
- Section of Plastic and Reconstructive Surgery. Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy; Plastic and Reconstructive Unit, Department of D.A.I. Chirurgico, Azienda Ospedaliera Universitaria Policlinico "Paolo Giaccone", 90127, Palermo, Italy
| | - Emanuele Cammarata
- Section of Plastic and Reconstructive Surgery. Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy; Plastic and Reconstructive Unit, Department of D.A.I. Chirurgico, Azienda Ospedaliera Universitaria Policlinico "Paolo Giaccone", 90127, Palermo, Italy
| | - Francesco Moschella
- BIOPLAST-Laboratory of BIOlogy and Regenerative Medicine-PLASTic Surgery, Plastic and Reconstructive Surgery Section, Department of Surgical, Oncological and Oral Sciences, University of Palermo, 90127 Palermo, Italy
| | - Adriana Cordova
- BIOPLAST-Laboratory of BIOlogy and Regenerative Medicine-PLASTic Surgery, Plastic and Reconstructive Surgery Section, Department of Surgical, Oncological and Oral Sciences, University of Palermo, 90127 Palermo, Italy; Section of Plastic and Reconstructive Surgery. Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy; Plastic and Reconstructive Unit, Department of D.A.I. Chirurgico, Azienda Ospedaliera Universitaria Policlinico "Paolo Giaccone", 90127, Palermo, Italy
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Castro VIB, Araújo AR, Duarte F, Sousa-Franco A, Reis RL, Pashkuleva I, Pires RA. Glycopeptide-Based Supramolecular Hydrogels Induce Differentiation of Adipose Stem Cells into Neural Lineages. ACS APPLIED MATERIALS & INTERFACES 2023. [PMID: 37327399 DOI: 10.1021/acsami.3c05309] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/18/2023]
Abstract
We applied a bottom-up approach to develop biofunctional supramolecular hydrogels from an aromatic glycodipeptide. The self-assembly of the glycopeptide was induced by either temperature manipulation (heating-cooling cycle) or solvent (DMSO to water) switch. The sol-gel transition was salt-triggered in cell culture media and resulted in gels with the same chemical compositions but different mechanical properties. Human adipose derived stem cells (hASCs) cultured on these gels under basal conditions (i.e., without differentiation factors) overexpressed neural markers, such as GFAP, Nestin, MAP2, and βIII-tubulin, confirming the differentiation into neural lineages. The mechanical properties of the gels influenced the number and distribution of the adhered cells. A comparison with gels obtained from the nonglycosylated peptide showed that glycosylation is crucial for the biofunctionality of the hydrogels by capturing and preserving essential growth factors, e.g., FGF-2.
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Affiliation(s)
- Vânia I B Castro
- 3B's Research Group, I3Bs─Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, 4805-017 Guimarães, Portugal
- ICVS/3B's─PT Government Associated Laboratory, 4805-017 Braga/Guimarães, Portugal
| | - Ana R Araújo
- 3B's Research Group, I3Bs─Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, 4805-017 Guimarães, Portugal
- ICVS/3B's─PT Government Associated Laboratory, 4805-017 Braga/Guimarães, Portugal
| | - Filipa Duarte
- 3B's Research Group, I3Bs─Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, 4805-017 Guimarães, Portugal
- ICVS/3B's─PT Government Associated Laboratory, 4805-017 Braga/Guimarães, Portugal
| | - António Sousa-Franco
- 3B's Research Group, I3Bs─Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, 4805-017 Guimarães, Portugal
- ICVS/3B's─PT Government Associated Laboratory, 4805-017 Braga/Guimarães, Portugal
| | - Rui L Reis
- 3B's Research Group, I3Bs─Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, 4805-017 Guimarães, Portugal
- ICVS/3B's─PT Government Associated Laboratory, 4805-017 Braga/Guimarães, Portugal
| | - Iva Pashkuleva
- 3B's Research Group, I3Bs─Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, 4805-017 Guimarães, Portugal
- ICVS/3B's─PT Government Associated Laboratory, 4805-017 Braga/Guimarães, Portugal
| | - Ricardo A Pires
- 3B's Research Group, I3Bs─Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, 4805-017 Guimarães, Portugal
- ICVS/3B's─PT Government Associated Laboratory, 4805-017 Braga/Guimarães, Portugal
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20
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Petrova V, Vachkova E. Outlook of Adipose-Derived Stem Cells: Challenges to Their Clinical Application in Horses. Vet Sci 2023; 10:vetsci10050348. [PMID: 37235430 DOI: 10.3390/vetsci10050348] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2023] [Revised: 05/05/2023] [Accepted: 05/11/2023] [Indexed: 05/28/2023] Open
Abstract
Adipose tissue is recognized as the major endocrine organ, potentially acting as a source of mesenchymal stem cells for various applications in regenerative medicine. Athletic horses are often exposed to traumatic injuries, resulting in severe financial losses. The development of adipose-derived stem cells' regenerative potential depends on many factors. The extraction of stem cells from subcutaneous adipose tissue is non-invasive, non-traumatic, cheaper, and safer than other sources. Since there is a lack of unique standards for identification, the isolated cells and applied differentiation protocols are often not species-specific; therefore, the cells cannot reveal their multipotent properties, so their stemness features remain questionable. The current review discusses some aspects of the specificity of equine adipose stem cells concerning their features, immunophenotyping, secretome profile, differentiation abilities, culturing conditions, and consequent possibilities for clinical application in concrete disorders. The presented new approaches elucidate the possibility of the transition from cell-based to cell-free therapy with regenerative purposes in horses as an alternative treatment to cellular therapy. In conclusion, their clinical benefits should not be underestimated due to the higher yield and the physiological properties of adipose-derived stem cells that facilitate the healing and tissue regeneration process and the ability to amplify the effects of traditional treatments. More profound studies are necessary to apply these innovative approaches when treating traumatic disorders in racing horses.
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Affiliation(s)
- Valeria Petrova
- Department of Pharmacology, Animal Physiology and Physiological Chemistry, Faculty of Veterinary Medicine, Trakia University, 6000 Stara Zagora, Bulgaria
| | - Ekaterina Vachkova
- Department of Pharmacology, Animal Physiology and Physiological Chemistry, Faculty of Veterinary Medicine, Trakia University, 6000 Stara Zagora, Bulgaria
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21
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Noureddine S, Nie J, Schneider A, Menon V, Fliesen Z, Dhahbi J, Victoria B, Oyer J, Robles-Carrillo L, Nunes ADDC, Ashiqueali S, Janusz A, Copik A, Robbins PD, Musi N, Masternak MM. microRNA-449a reduces growth hormone-stimulated senescent cell burden through PI3K-mTOR signaling. Proc Natl Acad Sci U S A 2023; 120:e2213207120. [PMID: 36976763 PMCID: PMC10083567 DOI: 10.1073/pnas.2213207120] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2022] [Accepted: 02/05/2023] [Indexed: 03/29/2023] Open
Abstract
Cellular senescence, a hallmark of aging, has been implicated in the pathogenesis of many major age-related disorders, including neurodegeneration, atherosclerosis, and metabolic disease. Therefore, investigating novel methods to reduce or delay the accumulation of senescent cells during aging may attenuate age-related pathologies. microRNA-449a-5p (miR-449a) is a small, noncoding RNA down-regulated with age in normal mice but maintained in long-living growth hormone (GH)-deficient Ames Dwarf (df/df) mice. We found increased fibroadipogenic precursor cells, adipose-derived stem cells, and miR-449a levels in visceral adipose tissue of long-living df/df mice. Gene target analysis and our functional study with miR-449a-5p have revealed its potential as a serotherapeutic. Here, we test the hypothesis that miR-449a reduces cellular senescence by targeting senescence-associated genes induced in response to strong mitogenic signals and other damaging stimuli. We demonstrated that GH downregulates miR-449a expression and accelerates senescence while miR-449a upregulation using mimetics reduces senescence, primarily through targeted reduction of p16Ink4a, p21Cip1, and the PI3K-mTOR signaling pathway. Our results demonstrate that miR-449a is important in modulating key signaling pathways that control cellular senescence and the progression of age-related pathologies.
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Affiliation(s)
- Sarah Noureddine
- Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL32827
| | - Jia Nie
- Sam and Ann Barshop Insititute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX78229
| | - Augusto Schneider
- Faculdade de Nutrição, Universidade Federal de Pelotas, 96010-610Pelotas, Brazil
| | - Vinal Menon
- Institute on the Biology of Aging and Metabolism, Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN55455
| | - Zoubeida Fliesen
- Department of Medical Education, School of Medicine, California University of Science & Medicine, Colton, CA92324
| | - Joseph Dhahbi
- Department of Medical Education, School of Medicine, California University of Science & Medicine, Colton, CA92324
| | - Berta Victoria
- Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL32827
| | - Jeremiah Oyer
- Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL32827
| | - Liza Robles-Carrillo
- Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL32827
| | - Allancer Divino De Carvalho Nunes
- Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL32827
- Institute on the Biology of Aging and Metabolism, Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN55455
| | - Sarah Ashiqueali
- Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL32827
| | - Artur Janusz
- Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL32827
- Celon Pharma Innovative Drugs Research & Development Department, Celon Pharma S.A., 05-152Kazun Nowy, Poland
| | - Alicja Copik
- Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL32827
| | - Paul D. Robbins
- Institute on the Biology of Aging and Metabolism, Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN55455
| | - Nicolas Musi
- Sam and Ann Barshop Insititute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX78229
- San Antonio Geriatric Research Education and Clinical Center (GRECC), South Texas Veterans Health Care System, San Antonio, TX78229
- Department of Medicine, Cedars Sinai Medical Center, LA90048
| | - Michal M. Masternak
- Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL32827
- Department of Head and Neck Surgery, Poznan University of Medical Sciences, 60-355Poznan, Poland
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22
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Szydlak R. Mesenchymal stem cells in ischemic tissue regeneration. World J Stem Cells 2023; 15:16-30. [PMID: 36909782 PMCID: PMC9993139 DOI: 10.4252/wjsc.v15.i2.16] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Revised: 11/10/2022] [Accepted: 01/19/2023] [Indexed: 02/21/2023] Open
Abstract
Diseases caused by ischemia are one of the leading causes of death in the world. Current therapies for treating acute myocardial infarction, ischemic stroke, and critical limb ischemia do not complete recovery. Regenerative therapies opens new therapeutic strategy in the treatment of ischemic disorders. Mesenchymal stem cells (MSCs) are the most promising option in the field of cell-based therapies, due to their secretory and immunomodulatory abilities, that contribute to ease inflammation and promote the regeneration of damaged tissues. This review presents the current knowledge of the mechanisms of action of MSCs and their therapeutic effects in the treatment of ischemic diseases, described on the basis of data from in vitro experiments and preclinical animal studies, and also summarize the effects of using these cells in clinical trial settings. Since the obtained therapeutic benefits are not always satisfactory, approaches aimed at enhancing the effect of MSCs in regenerative therapies are presented at the end.
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Affiliation(s)
- Renata Szydlak
- Chair of Medical Biochemistry, Faculty of Medicine, Jagiellonian University Medical College, Kraków 31-034, Poland
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23
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Manshori M, Kazemnejad S, Naderi N, Darzi M, Aboutaleb N, Golshahi H. Systemic delivery of menstrual blood stem cells is more effective in preventing remote organ injuries following myocardial infarction in comparison with bone marrow stem cells in rat. IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES 2023; 26:645-652. [PMID: 37275762 PMCID: PMC10237164 DOI: 10.22038/ijbms.2023.67574.14809] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Figures] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Accepted: 03/15/2023] [Indexed: 06/07/2023]
Abstract
Objectives Remote organ injury is a phenomenon that could happen following myocardial infarction (MI). We evaluated the potency of menstrual blood stromal (stem) cells (MenSCs) and bone marrow stem cells (BMSCs) to alleviate remote organ injuries following MI in rats. Materials and Methods 2 × 106 MenSCs or BMSCs were administrated seven days after MI induction via the tail vein. Four weeks after cell therapy, activities of aspartate aminotransferase (AST), urea, creatinine, and Blood Urea Nitrogen (BUN) were evaluated. The level of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 were determined by ELISA assay. The expression of Nuclear Factor-κB (NF-κB) was evaluated by immunohistochemical staining. Apoptosis activity and tissue damage were also determined by TUNEL and H&E staining, respectively. Results MenSCs and BMSCs administration caused a significant reduction in AST, urea, and BUN levels compared with the MI group. In addition, systemic injection of MenSCs significantly decreased the IL-1β level compared with BMSCs and MI groups (P<0.05 and P<0.01 respectively). Apoptosis in injured kidneys was noticeably diminished in MenSCs-treated rats compared with BMSCs administrated and MI groups (P<0.05 and P<0.05, respectively). In hepatic tissue, limited numbers of TUNEL-positive cells were detected in all groups. Interestingly, MenSCs therapy evoked inhibition of NF-κB in the kidney strikingly. Although, no significant NF-κB expression was observed in hepatic tissue in any group (P>0.05). Conclusion MenSCs are probably more protective than BMSCs on remote organ injuries following MI via decreasing cell death and immunoregulatory properties.
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Affiliation(s)
- Mahmood Manshori
- Nanobiotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran
| | - Somaieh Kazemnejad
- Nanobiotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran
| | - Nasim Naderi
- Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Maryam Darzi
- Nanobiotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran
| | - Nahid Aboutaleb
- Physiology Research Center, Iran University of Medical Sciences, Tehran, Iran
- Department of Physiology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Hannaneh Golshahi
- Nanobiotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran
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24
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Kazemi Asl S, Rahimzadegan M, Ostadrahimi R. The recent advancement in the chitosan hybrid-based scaffolds for cardiac regeneration after myocardial infarction. Carbohydr Polym 2023; 300:120266. [DOI: 10.1016/j.carbpol.2022.120266] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Revised: 10/08/2022] [Accepted: 10/23/2022] [Indexed: 11/07/2022]
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25
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Hu Y, Shao J, Shen L, Wang S, Xu K, Mao J, Shen J, Chen W. Protection of adipose-derived mesenchymal stromal cells during acute lung injury requires autophagy maintained by mTOR. Cell Death Dis 2022; 8:481. [PMID: 36470863 PMCID: PMC9722689 DOI: 10.1038/s41420-022-01267-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Revised: 09/15/2022] [Accepted: 11/18/2022] [Indexed: 12/10/2022]
Abstract
Previous studies suggest that mesenchymal stem cells may represent a promising cellular therapy for acute lung injury (ALI); however, the underlying relevant molecular mechanisms remain unclear. Adipose-derived mesenchymal stem cells (ADSCs) were isolated and characterized by alizarin red staining, oil red staining, and flow cytometry. Lung injury and inflammatory cell infiltration were determined using the Evans blue method, wet/dry weight ratio, and H&E staining. An ELISA was used to detect the concentrations of IFN-γ, IL-2, and TNF-α. Autophagy was detected with an mRFP-GFP-LC3 dual-fluorescence autophagy indicator system, Western blotting, and electron microscopy. We first demonstrated that ADSCs did alleviate the inflammatory responses and tissue damage in lipopolysaccharide (LPS)-induced ALI. Next, we further demonstrated in vivo that autophagy plays a key role in the maintenance of ADSC therapeutic efficacy. In vitro experiments demonstrated that ADSCs co-cultured with alveolar epithelial cells depend on autophagy for significant anti-inflammatory functions. Moreover, the mammalian target of rapamycin (mTOR) is a key regulator of autophagy. Taken together, our findings demonstrate that the effect of ADSC on ALI, especially on alveolar epithelial cells, is dependent on mTOR-mediated autophagy maintenance. The significance of our study for ALI therapy is discussed with respect to a more complete understanding of the therapeutic strategy paradigm.
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Affiliation(s)
- Yue Hu
- grid.412465.0Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, 310009 Hangzhou, Zhejiang China
| | - Jing Shao
- Cancer Institute of Integrated Traditional Chinese and Western Medicine, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province, 310012 Hangzhou, Zhejiang China
| | - Lanying Shen
- grid.412465.0Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, 310009 Hangzhou, Zhejiang China
| | - Shengchao Wang
- grid.13402.340000 0004 1759 700XDepartment of Gynecological Oncology, Women’s Hospital, Zhejiang University School of Medicine, 310006 Hangzhou, Zhejiang China
| | - Kaiyan Xu
- grid.412465.0Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, 310009 Hangzhou, Zhejiang China
| | - Jiayan Mao
- Cancer Institute of Integrated Traditional Chinese and Western Medicine, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province, 310012 Hangzhou, Zhejiang China
| | - Jian Shen
- Cancer Institute of Integrated Traditional Chinese and Western Medicine, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province, 310012 Hangzhou, Zhejiang China
| | - Wei Chen
- Cancer Institute of Integrated Traditional Chinese and Western Medicine, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province, 310012 Hangzhou, Zhejiang China
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26
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Interleukin-10-Modified Adipose-Derived Mesenchymal Stem Cells Prevent Hypertrophic Scar Formation via Regulating the Biological Characteristics of Fibroblasts and Inflammation. Mediators Inflamm 2022; 2022:6368311. [PMID: 35774067 PMCID: PMC9239815 DOI: 10.1155/2022/6368311] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2021] [Revised: 03/16/2022] [Accepted: 03/22/2022] [Indexed: 11/17/2022] Open
Abstract
Hypertrophic scar causes serious functional and cosmetic problem, but no treatment method is known to achieve a satisfactory therapeutic effect. However, mesenchymal stem cells show a possible cure prospect. Here, we investigated the effect of interleukin-10-modified adipose-derived mesenchymal stem cells (IL-10-ADMSC) on the formation of hypertrophic scar. In vitro, IL-10-ADMSC could highly express IL-10 and exhibited stronger inhibition of hypertrophic scar fibroblasts (HSFs) proliferation, migration, and extracellular matrix synthesis (the expression of collagen I, collagen III, FN, and α-SMA protein) than ADMSC. In vivo, we found that IL-10-ADMSC speeded up wound healing time and reduced scar area and scar outstanding height. Same as in vitro, IL-10-ADMSC also exhibited stronger inhibition of extracellular matrix synthesis (the expression of collagen I, collagen III protein) in wound than ADMSC. In addition, we also found that IL-10-ADMSC is also a stronger inhibitory effect on inflammation in wound than ADMSC, and IL-10-ADMSC inhibited TGF-β/Smads and NF-κB pathway. In conclusion, IL-10-ADMSC demonstrated the ability to prevent hypertrophic scar formation. And its possible molecular mechanism might be related to IL-10-ADMSC inhibiting the proliferation and migration of the synthesis of extracellular matrix of HSFs, and IL-10-ADMSC inhibited the inflammation during the wound healing.
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27
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Park JS, Kim D, Hong HS. Priming with a Combination of FGF2 and HGF Restores the Impaired Osteogenic Differentiation of Adipose-Derived Stem Cells. Cells 2022; 11:cells11132042. [PMID: 35805126 PMCID: PMC9265418 DOI: 10.3390/cells11132042] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Revised: 06/20/2022] [Accepted: 06/26/2022] [Indexed: 02/05/2023] Open
Abstract
Classical aging-associated diseases include osteoporosis, diabetes, hypertension, and arthritis. Osteoporosis causes the bone to become brittle, increasing fracture risk. Among the various treatments for fractures, stem cell transplantation is currently in the spotlight. Poor paracrine/differentiation capacity, owing to donor age or clinical history, limits efficacy. Lower levels of fibroblast growth factor 2 (FGF2) and hepatocyte growth factor (HGF) are involved in cell repopulation, angiogenesis, and bone formation in the elderly ADSCs (ADSC-E) than in the young ADSCs (ADSC-Y). Here, we study the effect of FGF2/HGF priming on the osteogenic potential of ADSC-E, determined by calcium deposition in vitro and ectopic bone formation in vivo. Age-induced FGF2/HGF deficiency was confirmed in ADSCs, and their supplementation enhanced the osteogenic differentiation ability of ADSC-E. Priming with FGF2/HGF caused an early shift of expression of osteogenic markers, including Runt-related transcription factor 2 (Runx-2), osterix, and alkaline phosphatase (ALP) during osteogenic differentiation. FGF2/HGF priming also created an environment favorable to osteogenesis by facilitating the secretion of bone morphogenetic protein 2 (BMP-2) and vascular endothelial growth factor (VEGF). Bone tissue of ADSC-E origin was observed in mice transplanted with FGF/HGF-primed ADSC-E. Collectively, FGF2/HGF priming could enhance the bone-forming capacity in ADSC-E. Therefore, growth factor-mediated cellular priming can enhance ADSC differentiation in bone diseases and thus contributes to the increased efficacy in vivo.
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Affiliation(s)
- Jeong Seop Park
- Department of Biomedical Science and Technology, Graduate School, Kyung Hee University, Seoul 02447, Korea; (J.S.P.); (D.K.)
| | - Doyoung Kim
- Department of Biomedical Science and Technology, Graduate School, Kyung Hee University, Seoul 02447, Korea; (J.S.P.); (D.K.)
| | - Hyun Sook Hong
- Department of Biomedical Science and Technology, Graduate School, Kyung Hee University, Seoul 02447, Korea; (J.S.P.); (D.K.)
- East-West Medical Research Institute, Kyung Hee University, Seoul 02447, Korea
- Kyung Hee Institute of Regenerative Medicine (KIRM), Medical Science Research Institute, Kyung Hee University Medical Center, Seoul 02447, Korea
- Correspondence: ; Tel.: +82-2-958-1828
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He M, Wang D, Xu Y, Jiang F, Zheng J, Feng Y, Cao J, Zhou X. Nitric Oxide-Releasing Platforms for Treating Cardiovascular Disease. Pharmaceutics 2022; 14:pharmaceutics14071345. [PMID: 35890241 PMCID: PMC9317153 DOI: 10.3390/pharmaceutics14071345] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2022] [Revised: 06/14/2022] [Accepted: 06/22/2022] [Indexed: 12/16/2022] Open
Abstract
Cardiovascular disease (CVD) is the first leading cause of death globally. Nitric oxide (NO) is an important signaling molecule that mediates diverse processes in the cardiovascular system, thereby providing a fundamental basis for NO-based therapy of CVD. At present, numerous prodrugs have been developed to release NO in vivo. However, the clinical application of these prodrugs still faces many problems, including the low payloads, burst release, and non-controlled delivery. To address these, various biomaterial-based platforms have been developed as the carriers to deliver NO to the targeted tissues in a controlled and sustained manner. This review aims to summarize recent developments of various therapeutic platforms, engineered to release NO for the treatment of CVD. In addition, two potential strategies to improve the effectiveness of existing NO therapy are also discussed, including the combination of NO-releasing platforms and either hydrogen sulfide-based therapy or stem cell therapy. Hopefully, some NO-releasing platforms may provide important therapeutic benefits for CVD.
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Affiliation(s)
- Mingyue He
- Department of Medical Imaging, Shanxi Medical University, Taiyuan 030001, China; (M.H.); (Y.X.)
| | - Deping Wang
- Key Laboratory of Cellular Physiology, Ministry of Education, The Department of Physiology, Shanxi Medical University, Taiyuan 030001, China; (D.W.); (F.J.); (J.Z.)
| | - Yumei Xu
- Department of Medical Imaging, Shanxi Medical University, Taiyuan 030001, China; (M.H.); (Y.X.)
| | - Fangying Jiang
- Key Laboratory of Cellular Physiology, Ministry of Education, The Department of Physiology, Shanxi Medical University, Taiyuan 030001, China; (D.W.); (F.J.); (J.Z.)
| | - Jian Zheng
- Key Laboratory of Cellular Physiology, Ministry of Education, The Department of Physiology, Shanxi Medical University, Taiyuan 030001, China; (D.W.); (F.J.); (J.Z.)
- Department of Breast Surgery, Shanxi Provincial Cancer Hospital, Shanxi Medical University, Taiyuan 030001, China
| | - Yanlin Feng
- Key Laboratory of Cellular Physiology, Ministry of Education, The Department of Physiology, Shanxi Medical University, Taiyuan 030001, China; (D.W.); (F.J.); (J.Z.)
- Correspondence: (Y.F.); (J.C.); (X.Z.)
| | - Jimin Cao
- Key Laboratory of Cellular Physiology, Ministry of Education, The Department of Physiology, Shanxi Medical University, Taiyuan 030001, China; (D.W.); (F.J.); (J.Z.)
- Correspondence: (Y.F.); (J.C.); (X.Z.)
| | - Xin Zhou
- Department of Medical Imaging, Shanxi Medical University, Taiyuan 030001, China; (M.H.); (Y.X.)
- Key Laboratory of Cellular Physiology, Ministry of Education, The Department of Physiology, Shanxi Medical University, Taiyuan 030001, China; (D.W.); (F.J.); (J.Z.)
- Correspondence: (Y.F.); (J.C.); (X.Z.)
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Wahba NS, Seliem AO, Abd Allah EG, Mohammed MZ. Electron microscopic study on the effect of chronic fluoxetine treatment on pituitary gland and the possible therapeutic effect of adipose-derived mesenchymal stem cells in adult male albino rats. Ultrastruct Pathol 2022; 46:334-347. [PMID: 35695512 DOI: 10.1080/01913123.2022.2083279] [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: 10/18/2022]
Abstract
BACKGROUND Adipose-derived mesenchymal stem cells (ADSCs) have therapeutic potential for the treatment of a variety of disorders due to their self-renewal and multipotential differentiation capabilities. AIM OF THE WORK This study was planned to demonstrate the electron microscopic structure of the pituitary gland after chronic fluoxetine treatment and the possible therapeutic effect of ADSCs. MATERIALS AND METHODS Thirty healthy male adult albino rats were classified into Control group (Group I). Fluoxetine treated (Group II) received 24 mg/kg/day of fluoxetine dissolved in 1.0 mL of tap water once a day. Fluoxetine group treated with ADSCs (Group III) received fluoxetine as group (II) for 30 days and then was injected once by ADSCs at a dose of 1 × 106 cells/rat in the tail vein suspended in 0.5 ml of phosphate-buffered saline (PBS). Recovery group (Group IV) received fluoxetine for 30 days and then received no treatment till the end of the experiment. RESULTS The ultrastructural observations of the fluoxetine-treated group revealed major histological changes in both the pars distalis and nervosa. Pars distalis revealed cells with different shapes, sizes, nuclei, and variable profiles of the cytoplasm. Pars nervosa, on the other hand, revealed pituicytes with electron-lucent cytoplasm and small apoptotic nuclei. Administration of ADSCs greatly improved the microscopic appearance of cells, while the recovery group showed similar histological changes as the fluoxetine group. CONCLUSION Fluoxetine caused various deleterious changes in the pituitary gland of albino rats, as evidenced by electron microscopy. These changes were almost corrected by the ADSCs treatment. .
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Affiliation(s)
- Nashwa S Wahba
- Department of Medical Histology and Cell Biology, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Assmaa O Seliem
- Department of Medical Histology and Cell Biology, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Enas G Abd Allah
- Department of Medical Histology and Cell Biology, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Maha Z Mohammed
- Department of Medical Histology and Cell Biology, Faculty of Medicine, Zagazig University, Zagazig, Egypt
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Narita S, Unno K, Kato K, Okuno Y, Sato Y, Tsumura Y, Fujikawa Y, Shimizu Y, Hayashida R, Kondo K, Shibata R, Murohara T. Direct reprogramming of adult adipose-derived regenerative cells toward cardiomyocytes using six transcriptional factors. iScience 2022; 25:104651. [PMID: 35811849 PMCID: PMC9263527 DOI: 10.1016/j.isci.2022.104651] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Revised: 04/30/2022] [Accepted: 06/16/2022] [Indexed: 10/29/2022] Open
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Yamaguchi S, Shimizu Y, Murohara T, Shibata R. Adipose-derived regenerative cells as a promising therapy for cardiovascular diseases: an overview. NAGOYA JOURNAL OF MEDICAL SCIENCE 2022; 84:208-215. [PMID: 35967953 PMCID: PMC9350562 DOI: 10.18999/nagjms.84.2.208] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/07/2021] [Accepted: 07/29/2021] [Indexed: 11/06/2022]
Abstract
The number of patients with ischemic cardiovascular diseases is significantly increasing as populations age. Therapeutic angiogenesis has been developed as a new treatment strategy for such patients. In recent years, the presence of mesenchymal stem cells in adipose tissues was reported, and regenerative medicine using these cells has attracted attention worldwide. In this review, we describe how the transplantation of adipose-derived regenerative cells enhances angiogenesis and tissue regeneration because of their multilineage potential and cytokine secretion. Then, the current status of therapeutic angiogenesis using adipose-derived regenerative cells in the field of cardiovascular medicine was also described. These cells present great advantages over bone marrow mononuclear cells, as these need easier, shorter, and less invasive preparations as well as less ethical concerns and immunological problems. The efficacy of adipose-derived regenerative cell transplantation in the treatment of various diseases was examined in several clinical trials with favorable results. Currently, a multicenter study of therapeutic angiogenesis using these cells is being conducted in patients with critical limb ischemia. In conclusion, we expect that this method will soon be established as a treatment for cardiovascular diseases that have been refractory to conventional treatments.
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Affiliation(s)
- Shukuro Yamaguchi
- Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yuki Shimizu
- Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Toyoaki Murohara
- Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Rei Shibata
- Department of Advanced Cardiovascular Therapeutics, Nagoya University Graduate School of Medicine, Nagoya, Japan
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Kashiyama N, Kormos RL, Matsumura Y, D'Amore A, Miyagawa S, Sawa Y, Wagner WR. Adipose-derived stem cell sheet under an elastic patch improves cardiac function in rats after myocardial infarction. J Thorac Cardiovasc Surg 2022; 163:e261-e272. [PMID: 32636026 DOI: 10.1016/j.jtcvs.2020.04.150] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2019] [Revised: 04/12/2020] [Accepted: 04/14/2020] [Indexed: 01/28/2023]
Abstract
OBJECTIVES Although adipose-derived stem cells (ADSCs) have shown promise in cardiac regeneration, stable engraftment is still challenging. Acellular bioengineered cardiac patches have shown promise in positively altering ventricular remodeling in ischemic cardiomyopathy. We hypothesized that combining an ADSC sheet approach with a bioengineered patch would enhance ADSC engraftment and positively promote cardiac function compared with either therapy alone in a rat ischemic cardiomyopathy model. METHODS Cardiac patches were generated from poly(ester carbonate urethane) urea and porcine decellularized cardiac extracellular matrix. ADSCs constitutively expressing green fluorescent protein were established from F344 rats and transplanted as a cell sheet over the left ventricle 3 days after left anterior descending artery ligation with or without an overlying cardiac patch. Cardiac function was serially evaluated using echocardiography for 8 weeks, comparing groups with combined cells and patch (group C, n = 9), ADSCs alone (group A, n = 7), patch alone (group P, n = 6) or sham groups (n = 7). RESULTS Much greater numbers of ADSCs survived in the C versus A groups (P < .01). At 8 weeks posttransplant, the percentage fibrotic area was lower (P < .01) in groups C and P compared with the other groups and vasculature in the peri-infarct zone was greater in group C versus other groups (P < .01), and hepatocyte growth factor expression was higher in group C than in other groups (P < .05). Left ventricular ejection fraction was higher in group C versus other groups. CONCLUSIONS A biodegradable cardiac patch enhanced ADSC engraftment, which was associated with greater cardiac function and neovascularization in the peri-infarct zone following subacute myocardial infarction.
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Affiliation(s)
- Noriyuki Kashiyama
- McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pa; Heart and Vascular Institute, University of Pittsburgh Medical Center, Pittsburgh, Pa; Department of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, Pa; Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita-city, Osaka, Japan
| | - Robert L Kormos
- McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pa; Heart and Vascular Institute, University of Pittsburgh Medical Center, Pittsburgh, Pa; Department of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, Pa
| | - Yasumoto Matsumura
- McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pa
| | - Antonio D'Amore
- McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pa; Fondazione RiMED, Palermo, Italy
| | - Shigeru Miyagawa
- Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita-city, Osaka, Japan
| | - Yoshiki Sawa
- Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita-city, Osaka, Japan
| | - William R Wagner
- McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pa; Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pa; Department of Surgery, University of Pittsburgh, Pittsburgh, Pa.
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Liu S, Zhang C, Hao J, Liu Y, Zheng S, Yang C, Yang J, Wu H. Icariin Promotes In Vitro Cardiomyocyte Proliferation and Differentiation in Human Bone Marrow-Derived Mesenchymal Stem Cells. J BIOMATER TISS ENG 2022. [DOI: 10.1166/jbt.2022.2924] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
Mesenchymal stem cells (MSCs) are the excellent candidates in myocardial regeneration given their easy accessibility, low immunogenicity and high potential for cardiomyocyte differentiation. This work focused on investigating the role of icariin, a main active component of the Traditional
Chinese herb epimedium, in human bone marrow-derived MSCs (BMSCs) proliferation and differentiation into cardiomyocytes In Vitro. Human BMSCs were cultivated In Vitro, and MTT assay was conducted to measure their proliferation. On this basis, we selected the optimal icariin dose
for promoting the proliferation to induce cardiomyocyte differentiation of MSCs, which were pretreated with or without 5-azacytidine (5-Aza). Cardiac-specific cardiac troponin I (cTnI) and connexin 43 (Cx43)-positive cells were detected by immunofluorescent staining. The differentiation ratio
of MSCs was examined by flow cytometry. This study measured early cardiac transcription factors (TFs) Nkx2.5 and GATA4 levels through RT-PCR and Western blotting (WB). As a result, icariin increased MSC proliferation dependent on its dose, and the optimal dose was determined to be 80 μg/l.
Furthermore, MSCs showed minimal cardiomyogenic differentiation when induced by icariin alone as confirmed by the expression of cardiac-related markers. Moreover, a synergic interaction was observed when icariin and 5-Aza cooperated to induce cardiomyocyte differentiation of MSCs. In conclusion,
Icariin stimulates proliferation and facilitates cardiomyocyte differentiation of MSCs In Vitro and may be potentially used as a new method for enhancing the MSCs efficacy in cardiovascular disease.
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Affiliation(s)
- Shaoying Liu
- Department of Cardiology, Beijing Hospital of Integrated Traditional Chinese and Western Medicine, Dongjie 3, Yongding Road, Haidian District, Beijing 100039, China
| | - Chengying Zhang
- Department of Cardiology, Traditional Chinese Medical Hospital of Beijing Huairou, 1 Houheng Jie, Huairou District, Beijing 101400, China
| | - Jing Hao
- Jimenli Community Health Service Center, Jimenli Community, Beisanhuan West Road, Haidian District, Beijing 100191, China
| | - Yuna Liu
- Department of Laboratory, Beijing Hospital of Integrated Traditional Chinese and Western Medicine, Dongjie 3, Yongding Road, Haidian District, Beijing 100039, China
| | - Sidao Zheng
- Department of Cardiology, Beijing Hospital of Integrated Traditional Chinese and Western Medicine, Dongjie 3, Yongding Road, Haidian District, Beijing 100039, China
| | - Cui Yang
- Department of Cardiology, Traditional Chinese Medical Hospital of Beijing Huairou, 1 Houheng Jie, Huairou District, Beijing 101400, China
| | - Jiyuan Yang
- Department of Cardiology, Beijing Hospital of Integrated Traditional Chinese and Western Medicine, Dongjie 3, Yongding Road, Haidian District, Beijing 100039, China
| | - Hongjin Wu
- Beijing Haidian Hospital, Haidian Section of Peking University Third Hospital, 29 Zhongguancun Dajie, Haidian District, Beijing 100080, China
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Shibu MA, Lin YJ, Chiang CY, Lu CY, Goswami D, Sundhar N, Agarwal S, Islam MN, Lin PY, Lin SZ, Ho TJ, Tsai WT, Kuo WW, Huang CY. Novel anti-aging herbal formulation Jing Si displays pleiotropic effects against aging associated disorders. Pharmacotherapy 2022; 146:112427. [DOI: 10.1016/j.biopha.2021.112427] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Revised: 11/02/2021] [Accepted: 11/12/2021] [Indexed: 01/07/2023]
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Trébol J, Georgiev-Hristov T, Pascual-Miguelañez I, Guadalajara H, García-Arranz M, García-Olmo D. Stem cell therapy applied for digestive anastomosis: Current state and future perspectives. World J Stem Cells 2022; 14:117-141. [PMID: 35126832 PMCID: PMC8788180 DOI: 10.4252/wjsc.v14.i1.117] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Revised: 06/21/2021] [Accepted: 12/31/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Digestive tract resections are usually followed by an anastomosis. Anastomotic leakage, normally due to failed healing, is the most feared complication in digestive surgery because it is associated with high morbidity and mortality. Despite technical and technological advances and focused research, its rates have remained almost unchanged the last decades. In the last two decades, stem cells (SCs) have been shown to enhance healing in animal and human studies; hence, SCs have emerged since 2008 as an alternative to improve anastomoses outcomes.
AIM To summarise the published knowledge of SC utilisation as a preventative tool for hollow digestive viscera anastomotic or suture leaks.
METHODS PubMed, Science Direct, Scopus and Cochrane searches were performed using the key words “anastomosis”, “colorectal/colonic anastomoses”, “anastomotic leak”, “stem cells”, “progenitor cells”, “cellular therapy” and “cell therapy” in order to identify relevant articles published in English and Spanish during the years of 2000 to 2021. Studies employing SCs, performing digestive anastomoses in hollow viscera or digestive perforation sutures and monitoring healing were finally included. Reference lists from the selected articles were reviewed to identify additional pertinent articles.
Given the great variability in the study designs, anastomotic models, interventions (SCs, doses and vehicles) and outcome measures, performing a reliable meta-analysis was considered impossible, so we present the studies, their results and limitations.
RESULTS Eighteen preclinical studies and three review papers were identified; no clinical studies have been published and there are no registered clinical trials. Experimental studies, mainly in rat and porcine models and occasionally in very adverse conditions such as ischaemia or colitis, have been demonstrated SCs as safe and have shown some encouraging morphological, functional and even clinical results. Mesenchymal SCs are mostly employed, and delivery routes are mainly local injections and cell sheets followed by biosutures (sutures coated by SCs) or purely topical. As potential weaknesses, animal models need to be improved to make them more comparable and equivalent to clinical practice, and the SC isolation processes need to be standardised. There is notable heterogeneity in the studies, making them difficult to compare. Further investigations are needed to establish the indications, the administration system, potential adjuvants, the final efficacy and to confirm safety and exclude definitively oncological concerns.
CONCLUSION The future role of SC therapy to induce healing processes in digestive anastomoses/sutures still needs to be determined and seems to be currently far from clinical use.
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Affiliation(s)
- Jacobo Trébol
- Servicio de Cirugía General y del Aparato Digestivo, Complejo Asistencial Universitario de Salamanca, Salamanca 37007, Spain
- Departamento de Anatomía e Histología Humanas, Universidad de Salamanca, Salamanca 37007, Spain
| | - Tihomir Georgiev-Hristov
- Servicio de Cirugía General y del Aparato Digestivo, Hospital General Universitario de Villalba, Madrid 28400, Spain
| | - Isabel Pascual-Miguelañez
- Servicio de Cirugía General y del Aparato Digestivo, Hospital Universitario La Paz, Madrid 28046, Spain
| | - Hector Guadalajara
- Servicio de Cirugía General y del Aparato Digestivo, Hospital Universitario Fundación Jiménez Díaz, Madrid 28040, Spain
| | - Mariano García-Arranz
- Grupo de Investigación en Nuevas Terapias, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz, Madrid 28040, Spain
- Departamento de Cirugía, Universidad Autónoma de Madrid, Madrid 28029, Spain
| | - Damian García-Olmo
- Departamento de Cirugía, Universidad Autónoma de Madrid, Madrid 28029, Spain
- Servicio de Cirugía General y del Aparato Digestivo, Hospital Universitario Fundación Jiménez Díaz y Grupo Quiron-Salud Madrid, Madrid 28040, Spain
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Khalighi S, Saadatmand M. Bioprinting a thick and cell-laden partially oxidized alginate-gelatin scaffold with embedded micro-channels as future soft tissue platform. Int J Biol Macromol 2021; 193:2153-2164. [PMID: 34800519 DOI: 10.1016/j.ijbiomac.2021.11.046] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2021] [Revised: 11/03/2021] [Accepted: 11/05/2021] [Indexed: 11/24/2022]
Abstract
Despite all the advancements in tissue engineering, one of the unsolved challenges is the mass transfer limitation. Therefore, the subject of pre-vascularization in the engineered tissues gets more attention to avoid necrotic core formation. In this study, we considered a design for interconnected channels with a muscle tissue-like structure, in silico and in vitro. A sequence of simple steps make it possible for us to use the same material, gelatin, as both a sacrificial material and one of the main components of the scaffold simultaneously. We defined a new approach to quantify the repeatability of a new combination of hydrogels (Partially Oxidized Alginate + Gelatin) for extrusion-based bioprinting. Additionally, the mechanical properties, hydrogel porosity, degradation time, and swelling ratio were also evaluated. Based on all these test results, the scaffold with the optimum properties was chosen for the bioprinting of adipose derived mesenchymal stem cells (ADMSCs) in the scaffolds with and without the channels. This bioprinted scaffold with microchannels showed promising mimicry of the microenvironment, leading to higher survival and proliferation rates of the cells by up to 250%. Based on these results, it has the potential to serve as a platform for further research in vascularization, healthy/disease modelling, and stem cell differentiation.
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Affiliation(s)
- Sadaf Khalighi
- Department of Chemical and Petroleum Engineering, Sharif University of Technology, Tehran, Iran
| | - Maryam Saadatmand
- Department of Chemical and Petroleum Engineering, Sharif University of Technology, Tehran, Iran.
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Gazor R, Asgari M, Abdollajhifar MA, Kiani P, Zare F, Fadaei Fathabady F, Norouzian M, Amini A, Khosravipour A, Atashgah RB, Kazemi M, Chien S, Bayat M. Simultaneous Treatment of Photobiomodulation and Demineralized Bone Matrix With Adipose-Derived Stem Cells Improve Bone Healing in an osteoporotic bone defect. J Lasers Med Sci 2021; 12:e41. [PMID: 34733764 DOI: 10.34172/jlms.2021.41] [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] [Received: 05/30/2020] [Accepted: 09/23/2020] [Indexed: 12/28/2022]
Abstract
Introduction: The ability of simultaneous treatment of critical-sized femoral defects (CSFDs) with photobiomodulation (PBM) and demineralized bone matrix (DBM) with or without seeded adipose-derived stem cells (ASCs) to induce bone reconstruction in ovariectomized induced osteoporotic (OVX) rats was investigated. Methods: The OVX rats with CSFD were arbitrarily separated into 6 groups: control, scaffold (S, DBM), S + PBM, S + alendronate (ALN), S + ASCs, and S + PBM + ASCs. Each group was assessed by cone beam computed tomography (CBCT) and histological examinations. Results: In the fourth week, CBCT and histological analyses revealed that the largest volume of new bone formed in the S + PBM and S + PBM + ASC groups. The S + PBM treatment relative to the S and S + ALN treatments remarkably reduced the CSFD (Mann-Whitney test, P = 0.009 and P = 0.01). Furthermore, S + PBM + ASCs treatment compared to the S and S + ALN treatments significantly decreased CSFD (Mann Whitney test, P = 0.01). In the eighth week, CBCT analysis showed that extremely enhanced bone regeneration occurred in the CSFD of the S + PBM group. Moreover, the CSFD in the S + PBM group was substantially smaller than S, S + ALN and S + ASCs groups (Mann Whitney test, P = 0.01, P = 0.02 and P = 0.009). Histological observations showed more new bone formation in the treated CSFD of S + PBM + ASCs and S + PBM groups. Conclusion: The PBM plus DBM with or without ASCs significantly enhanced bone healing in the CSFD in OVX rats compared to control, DBM alone, and ALN plus DBM groups. The PBM plus DBM with or without ASCs significantly decreased the CSFD area compared to either the solo DBM or ALN plus DBM treatments.
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Affiliation(s)
- Rouhallah Gazor
- Department of Anatomy and Cell Biology, Faculty of Medicine, Guilan University of Medical Sciences, Rasht, Iran
| | - Mehrdad Asgari
- Department of Anatomy and Cell Biology, Faculty of Medicine, Guilan University of Medical Sciences, Rasht, Iran.,Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; And Department of Maxillofacial Radiology, Guilan University of Medical Sciences, Rasht, Guilan, Iran
| | - Mohammad-Amin Abdollajhifar
- Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Pejman Kiani
- Department of Neuroscience and Addiction Studies, School of Advanced Technologies in Medicine, Tehran University of Medical Science, Tehran, Iran
| | - Fatemeh Zare
- Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fatemeh Fadaei Fathabady
- Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohsen Norouzian
- Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Abdollah Amini
- Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Armin Khosravipour
- Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Rahimeh B Atashgah
- Department of Pharmaceutical Biomaterials, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, 13169- 43551, Iran
| | - Mahsa Kazemi
- Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sufan Chien
- Price Institute of Surgical Research, University of Louisville, and Noveratech LLC, Louisville, Kentucky; USA
| | - Mohammad Bayat
- Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.,Price Institute of Surgical Research, University of Louisville, and Noveratech LLC, Louisville, Kentucky; USA
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Angiogenic Effects and Crosstalk of Adipose-Derived Mesenchymal Stem/Stromal Cells and Their Extracellular Vesicles with Endothelial Cells. Int J Mol Sci 2021; 22:ijms221910890. [PMID: 34639228 PMCID: PMC8509224 DOI: 10.3390/ijms221910890] [Citation(s) in RCA: 40] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2021] [Revised: 10/02/2021] [Accepted: 10/04/2021] [Indexed: 12/13/2022] Open
Abstract
Adipose-derived mesenchymal stem/stromal cells (ASCs) are an adult stem cell population able to self-renew and differentiate into numerous cell lineages. ASCs provide a promising future for therapeutic angiogenesis due to their ability to promote blood vessel formation. Specifically, their ability to differentiate into endothelial cells (ECs) and pericyte-like cells and to secrete angiogenesis-promoting growth factors and extracellular vesicles (EVs) makes them an ideal option in cell therapy and in regenerative medicine in conditions including tissue ischemia. In recent angiogenesis research, ASCs have often been co-cultured with an endothelial cell (EC) type in order to form mature vessel-like networks in specific culture conditions. In this review, we introduce co-culture systems and co-transplantation studies between ASCs and ECs. In co-cultures, the cells communicate via direct cell-cell contact or via paracrine signaling. Most often, ASCs are found in the perivascular niche lining the vessels, where they stabilize the vascular structures and express common pericyte surface proteins. In co-cultures, ASCs modulate endothelial cells and induce angiogenesis by promoting tube formation, partly via secretion of EVs. In vivo co-transplantation of ASCs and ECs showed improved formation of functional vessels over a single cell type transplantation. Adipose tissue as a cell source for both mesenchymal stem cells and ECs for co-transplantation serves as a prominent option for therapeutic angiogenesis and blood perfusion in vivo.
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Gong H, Wang T, Xu Q. Resident stem cells in the heart. MEDICAL REVIEW (BERLIN, GERMANY) 2021; 1:10-13. [PMID: 37724080 PMCID: PMC10471108 DOI: 10.1515/mr-2021-0003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Accepted: 06/18/2021] [Indexed: 09/20/2023]
Abstract
Cardiovascular disease is the leading cause of mobility and morality worldwide, in which the ischemic heart disease is the most common type of the diseases. During last decade, a major progress in the study of the pathogenesis of heart disease has been achieved. For example, the discovery of adult stem/progenitor cells in the heart and vessel tissues may play a role in tissue regeneration. However, the issue of 31 retractions for cardiac stem cell work has caused a "storm of trust" in the heart stem cell field, in which both founders and scientists have become cautious and conservative in stem cell research of the heart. Despite that the existence of adult cardiac stem cells has been denied, recent studies confirmed that there are many other resident stem/progenitor cells in adult heart. Although these cells cannot differentiate into cardiomyocytes, the role they played in heart repair after injury should not be ignored. The purpose of this short article is to briefly review the current research progress in resident stem/progenitor cells in the heart, to discuss how they function during cardiac repair and to point out unanswered questions in the research field.
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Affiliation(s)
- Hui Gong
- Department of Cardiology,
The First Affiliated Hospital,
Zhejiang University School of Medicine, Hangzhou,
Zhejiang, China
| | - Ting Wang
- Department of Cardiology,
The First Affiliated Hospital,
Zhejiang University School of Medicine, Hangzhou,
Zhejiang, China
| | - Qingbo Xu
- Department of Cardiology,
The First Affiliated Hospital,
Zhejiang University School of Medicine, Hangzhou,
Zhejiang, China
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Advancing Regenerative Medicine Through the Development of Scaffold, Cell Biology, Biomaterials and Strategies of Smart Material. REGENERATIVE ENGINEERING AND TRANSLATIONAL MEDICINE 2021. [DOI: 10.1007/s40883-021-00227-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
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Huang LH, Rau CS, Wu SC, Wu YC, Wu CJ, Tsai CW, Lin CW, Lu TH, Hsieh CH. Identification and characterization of hADSC-derived exosome proteins from different isolation methods. J Cell Mol Med 2021; 25:7436-7450. [PMID: 34235869 PMCID: PMC8335681 DOI: 10.1111/jcmm.16775] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2020] [Revised: 06/10/2021] [Accepted: 06/21/2021] [Indexed: 02/06/2023] Open
Abstract
Exosomes are secreted into the extracellular space by most cell types and contain various molecular constituents, which play roles in many biological processes. Adipose-derived mesenchymal stem cells (ADSCs) can differentiate into a variety of cell types and secrete a series of paracrine factors through exosomes. ADSC-derived exosomes have shown diagnostic and therapeutic potential in many clinical diseases. The molecular components are critical for their mechanisms. Several methods have been developed for exosome purification, including ultracentrifugation, ultrafiltration, density gradient purification, size-based isolation, polymer precipitation and immuno-affinity purification. Thus, we employed four methods to isolate exosomes from the hADSC culture medium, including ultracentrifugation, size exclusion chromatography, ExoQuick-TC precipitation and ExoQuick-TC ULTRA isolation. Following exosome isolation, we performed quantitative proteomic analysis of the exosome proteins using isobaric tags for relative and absolute quantification (iTRAQ) labelling, combined with 2D-LC-MS/MS. There were 599 universal and 138 stably expressed proteins in hADSC-derived exosomes. We proved that these proteins were potential hADSC-derived exosomes markers, including CD109, CD166, HSPA4, TRAP1, RAB2A, RAB11B and RAB14. From the quantitative proteomic analysis, we demonstrated that hADSC-derived exosome protein expression varied, with lipopolysaccharide (LPS) treatment, in the different isolation methods. Pathway analysis and proliferation, migration and endothelial tube formation assays showed varying effects in cells stimulated with hADSC-derived exosomes from different isolation methods. Our study revealed that different isolation methods might introduce variations in the protein composition in exosomes, which reflects their effects on biological function. The pros and cons of these methods are important points to consider for downstream research applications.
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Affiliation(s)
- Lien-Hung Huang
- Department of Neurosurgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Cheng-Shyuan Rau
- Department of Neurosurgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Shao-Chun Wu
- Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Yi-Chan Wu
- Department of Plastic Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chia-Jung Wu
- Department of Plastic Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chia-Wen Tsai
- Department of Plastic Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chia-Wei Lin
- Department of Plastic Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Tsu-Hsiang Lu
- Department of Plastic Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Ching-Hua Hsieh
- Department of Plastic Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
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Dong W, Song Z, Liu S, Yu P, Shen Z, Yang J, Yang D, Hu Q, Zhang H, Gu Y. Adipose-Derived Stem Cells Based on Electrospun Biomimetic Scaffold Mediated Endothelial Differentiation Facilitating Regeneration and Repair of Abdominal Wall Defects via HIF-1α/VEGF Pathway. Front Bioeng Biotechnol 2021; 9:676409. [PMID: 34307320 PMCID: PMC8293919 DOI: 10.3389/fbioe.2021.676409] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2021] [Accepted: 06/18/2021] [Indexed: 11/26/2022] Open
Abstract
Application of synthetic or biological meshes is the main therapy for the repair and reconstruction of abdominal wall defects, a common disease in surgery. Currently, no ideal materials are available, and there is an urgent need to find appropriate ones to satisfy clinical needs. Electrospun scaffolds have drawn attention in soft tissue reconstruction. In this study, we developed a novel method to fabricate a composite electrospun scaffold using a thermoresponsive hydrogel, poly (N-isopropylacrylamide)-block-poly (ethylene glycol), and a biodegradable polymer, polylactic acid (PLA). This scaffold provided not only a high surface area/volume ratio and a three-dimensional fibrous matrix but also high biocompatibility and sufficient mechanical strength, and could simulate the native extracellular matrix and accelerate cell adhesion and proliferation. Furthermore, rat adipose-derived stem cells (ADSCs) were seeded in the composite electrospun scaffold to enhance the defect repair and regeneration by directionally inducing ADSCs into endothelial cells. In addition, we found early vascularization in the process was regulated by the hypoxia inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) pathway. In our study, overexpression of HIF-1α/VEGF in ADSCs using a lentivirus system promoted early vascularization in the electrospun scaffolds. Overall, we expect our composite biomimetic scaffold method will be applicable and useful in abdominal wall defect regeneration and repair in the future.
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Affiliation(s)
- Wenpei Dong
- Department of General Surgery, Hernia and Abdominal Wall Surgery Center of Shanghai Jiao Tong University, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhicheng Song
- Department of General Surgery, Hernia and Abdominal Wall Surgery Center of Shanghai Jiao Tong University, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Suihong Liu
- Rapid Manufacturing Engineering Center, Shanghai University, Shanghai, China
| | - Ping Yu
- Department of Pharmacy, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhipeng Shen
- Rapid Manufacturing Engineering Center, Shanghai University, Shanghai, China
| | - Jianjun Yang
- Department of General Surgery, Hernia and Abdominal Wall Surgery Center of Shanghai Jiao Tong University, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Dongchao Yang
- Department of General Surgery, Hernia and Abdominal Wall Surgery Center of Shanghai Jiao Tong University, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qinxi Hu
- Rapid Manufacturing Engineering Center, Shanghai University, Shanghai, China
| | - Haiguang Zhang
- Rapid Manufacturing Engineering Center, Shanghai University, Shanghai, China
| | - Yan Gu
- Department of General Surgery, Hernia and Abdominal Wall Surgery Center of Shanghai Jiao Tong University, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Maturation strategies and limitations of induced pluripotent stem cell-derived cardiomyocytes. Biosci Rep 2021; 41:226678. [PMID: 33057659 PMCID: PMC8209171 DOI: 10.1042/bsr20200833] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Revised: 10/06/2020] [Accepted: 10/12/2020] [Indexed: 12/14/2022] Open
Abstract
Induced pluripotent stem cells (iPSCs) have the ability to differentiate into cardiomyocytes (CMs). They are not only widely used in cardiac pharmacology screening, human heart disease modeling, and cell transplantation-based treatments, but also the most promising source of CMs for experimental and clinical applications. However, their use is largely restricted by the immature phenotype of structure and function, which is similar to embryonic or fetal CMs and has certain differences from adult CMs. In order to overcome this critical issue, many studies have explored and revealed new strategies to induce the maturity of iPSC-CMs. Therefore, this article aims to review recent induction methods of mature iPSC-CMs, related mechanisms, and limitations.
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Qin F, Zhang W, Zhang M, Long X, Si L, Li Z, Huang J, Wang X. Adipose-Derived Stem Cells Improve the Aging Skin of Nude Mice by Promoting Angiogenesis and Reducing Local Tissue Water. Aesthet Surg J 2021; 41:NP905-NP913. [PMID: 33428732 DOI: 10.1093/asj/sjab001] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Adipose-derived stem cells (ASCs) are considered promising cells for skin rejuvenation. However, whether the angiogenetic effect of ASCs plays an important role in the treatment of aging skin and its influence on skin tissue remain elusive. OBJECTIVES The aim of this study was to evaluate the effect of ASCs on angiogenesis and local tissue water (LTW) in the aging skin of nude mice. METHODS Twelve nude mice were randomly divided into a UVB-induced photoaging group and a natural aging group. After the mouse model had been established, ASCs and phosphate-buffered saline (PBS) were then each injected into different sides of the dorsal skin of the mice. Blood perfusion and LTW content were measured. After 7 weeks, mice were killed, and skin samples were collected to measure the thickness of the dermis, the density of the capillaries, and the expression of angiogenic growth factors. RESULTS ASC therapy significantly increased the thickness of the dermis, the number of capillaries, and the expression of some angiogenic growth factors (vascular endothelial growth factor, insulin-like growth factor 1, and epidermal growth factor). At 7 weeks after injection, blood perfusion was significantly higher on the side injected with ASCs than on the side injected with PBS. LTW content was increased in the PBS-injected side, but the ASC-injected side showed no significant changes over time. CONCLUSIONS ASCs increased dermal thickness, promoted angiogenesis, and reduced LTW content in the skin of photoaging mice, providing a potential clinical therapy for skin rejuvenation.
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Affiliation(s)
- Feng Qin
- Department of Plastic Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China
| | - Wenchao Zhang
- Department of Plastic Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China
| | - Mingzi Zhang
- Department of Plastic Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China
| | - Xiao Long
- Department of Plastic Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China
| | - Loubin Si
- Department of Plastic Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China
| | - Zhenjiang Li
- Department of Vascular Surgery, First Affiliated Hospital of the Medical School of Zhejiang University, Hangzhou, China
| | - Jiuzuo Huang
- Department of Plastic Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China
| | - Xiaojun Wang
- Department of Plastic Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China
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Kim JY, Park EJ, Kim SM, Lee HJ. Optimization of adipogenic differentiation conditions for canine adipose-derived stem cells. J Vet Sci 2021; 22:e53. [PMID: 34170094 PMCID: PMC8318799 DOI: 10.4142/jvs.2021.22.e53] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Revised: 05/24/2021] [Accepted: 06/04/2021] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND Canine adipose-derived stem cells (cADSCs) exhibit various differentiation properties and are isolated from the canine subcutaneous fat. Although cADSCs are valuable as tools for research on adipogenic differentiation, studies focusing on adipogenic differentiation methods and the underlying mechanisms are still lacking. OBJECTIVES In this study, we aimed to establish an optimal method for adipogenic differentiation conditions of cADSCs and evaluate the role of peroxisome proliferator-activated receptor gamma (PPARγ) and estrogen receptor (ER) signaling in the adipogenic differentiation. METHODS To induce adipogenic differentiation of cADSCs, 3 different adipogenic medium conditions, MDI, DRI, and MDRI, using 3-isobutyl-1-methylxanthine (M), dexamethasone (D), insulin (I), and rosiglitazone (R) were tested. RESULTS MDRI, addition of PPARγ agonist rosiglitazone to MDI, was the most significantly facilitated cADSC into adipocyte. GW9662, an antagonist of PPARγ, significantly reduced adipogenic differentiation induced by rosiglitazone. Adipogenic differentiation was also stimulated when 17β-estradiol was added to MDI and DRI, and this stimulation was inhibited by the ER antagonist ICI182,780. CONCLUSIONS Taken together, our results suggest that PPARγ and ER signaling are related to the adipogenic differentiation of cADSCs. This study could provide basic information for future research on obesity or anti-obesity mechanisms in dogs.
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Affiliation(s)
- Jong Yeon Kim
- Department of Food and Nutrition, College of BioNano Technology, Gachon University, Seongnam 13120, Korea
| | - Eun Jung Park
- Department of Food and Nutrition, College of BioNano Technology, Gachon University, Seongnam 13120, Korea.,Institute for Aging and Clinical Nutrition Research, Gachon University, Seongnam 13120, Korea
| | - Sung Min Kim
- Department of Food and Nutrition, College of BioNano Technology, Gachon University, Seongnam 13120, Korea.,Institute for Aging and Clinical Nutrition Research, Gachon University, Seongnam 13120, Korea
| | - Hae Jeung Lee
- Department of Food and Nutrition, College of BioNano Technology, Gachon University, Seongnam 13120, Korea.,Institute for Aging and Clinical Nutrition Research, Gachon University, Seongnam 13120, Korea.
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Ji Y, Ma Y, Shen J, Ni H, Lu Y, Zhang Y, Ma H, Liu C, Zhao Y, Ding S, Xiang M, Xie Y. TBX20 Contributes to Balancing the Differentiation of Perivascular Adipose-Derived Stem Cells to Vascular Lineages and Neointimal Hyperplasia. Front Cell Dev Biol 2021; 9:662704. [PMID: 34150759 PMCID: PMC8206642 DOI: 10.3389/fcell.2021.662704] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Accepted: 04/21/2021] [Indexed: 11/13/2022] Open
Abstract
Background Perivascular adipose-derived stem cells (PVASCs) can contribute to vascular remodeling, which are also capable of differentiating into multiple cell lineages. The present study aims to investigate the mechanism of PVASC differentiation toward smooth muscle cells (SMCs) and endothelial cells (ECs) as well as its function in neointimal hyperplasia. Methods Single-cell sequencing and bulk mRNA sequencing were applied for searching key genes in PVASC regarding its role in vascular remodeling. PVASCs were induced to differentiate toward SMCs and ECs in vitro, which was quantitatively evaluated using immunofluorescence, quantitative real-time PCR (QPCR), and Western blot. Lentivirus transfections were performed in PVASCs to knock down or overexpress TBX20. In vivo, PVASCs transfected with lentivirus were transplanted around the guidewire injured femoral artery. Hematoxylin-eosin (H&E) staining was performed to examine their effects on neointimal hyperplasia. Results Bulk mRNA sequencing and single-cell sequencing revealed a unique expression of TBX20 in PVASCs. TBX20 expression markedly decreased during smooth muscle differentiation while it increased during endothelial differentiation of PVASCs. TBX20 knockdown resulted in the upregulation of SMC-specific marker expression and activated Smad2/3 signaling, while inhibiting endothelial differentiation. In contrast, TBX20 overexpression repressed the differentiation of PVASCs toward smooth muscle cells but promoted endothelial differentiation in vitro. Transplantation of PVASCs transfected with TBX20 overexpression lentivirus inhibited neointimal hyperplasia in a murine femoral artery guidewire injury model. On the contrary, neointimal hyperplasia significantly increased in the TBX20 knockdown group. Conclusion A subpopulation of PVASCs uniquely expressed TBX20. TBX20 could regulate SMC and EC differentiation of PVASCs in vitro. Transplantation of PVASCs after vascular injury suggested that PVASCs participated in neointimal hyperplasia via TBX20.
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Affiliation(s)
- Yongli Ji
- Department of Cardiology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | - Yuankun Ma
- Department of Cardiology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | - Jian Shen
- Department of Cardiology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | - Hui Ni
- Department of Cardiology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | - Yunrui Lu
- Department of Cardiology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | - Yuhao Zhang
- Department of Cardiology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | - Hong Ma
- Department of Cardiology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | - Chang Liu
- Department of Cardiology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | - Yiming Zhao
- Department of Endocrinology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | - Siyin Ding
- Department of Cardiology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | - Meixiang Xiang
- Department of Cardiology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | - Yao Xie
- Department of Cardiology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
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Biotherapeutic-loaded injectable hydrogels as a synergistic strategy to support myocardial repair after myocardial infarction. J Control Release 2021; 335:216-236. [PMID: 34022323 DOI: 10.1016/j.jconrel.2021.05.023] [Citation(s) in RCA: 58] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Revised: 05/16/2021] [Accepted: 05/18/2021] [Indexed: 12/18/2022]
Abstract
Myocardial infarction (MI) has been considered as the leading cause of cardiovascular-related deaths worldwide. Although traditional therapeutic agents including various bioactive species such as growth factors, stem cells, and nucleic acids have demonstrated somewhat usefulness for the restoration of cardiac functions, the therapeutic efficiency remains unsatisfactory most likely due to the off-target-associated side effects and low localized retention of the used therapeutic agents in the infarcted myocardium, which constitutes a substantial barrier for the effective treatment of MI. Injectable hydrogels are regarded as a minimally invasive technology that can overcome the clinical and surgical limitations of traditional stenting by a modulated sol-gel transition and localized transport of a variety of encapsulated cargoes, leading to enhanced therapeutic efficiency and improved patient comfort and compliance. However, the design of injectable hydrogels for myocardial repair and the mechanism of action of bioactive substance-loaded hydrogels for MI repair remain unclear. To elucidate these points, we summarized the recent progresses made on the use of injectable hydrogels for encapsulation of various therapeutic substances for MI treatment with an emphasis on the mechanism of action of hydrogel systems for myocardial repair. Specifically, the pathogenesis of MI and the rational design of injectable hydrogels for myocardial repair were presented. Next, the mechanisms of various biotherapeutic substance-loaded injectable hydrogels for myocardial repair was discussed. Finally, the potential challenges and future prospects for the use of injectable hydrogels for MI treatment were proposed for the purpose of drawing theoretical guidance on the development of novel therapeutic strategies for efficient treatment of MI.
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Exosomes from Adipose Mesenchymal Stem Cells Overexpressing Stanniocalcin-1 Promote Reendothelialization After Carotid Endarterium Mechanical Injury. Stem Cell Rev Rep 2021; 18:1041-1053. [PMID: 33982245 DOI: 10.1007/s12015-021-10180-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/03/2021] [Indexed: 02/07/2023]
Abstract
OBJECTIVE Stanniocalcin-1 (STC-1) is a secreted glycoprotein that participates in the regulation of inflammation, apoptosis, and necrosis. We investigated the reendothelialization effect of exosomes from adipose stem cells (ADSC) overexpressing STC-1 on injured carotid endarterium. METHODS ADSCs were transfected with lentivirus vectors containing pre-STC-1. PHK-26 as molecular probe was used to track the exosomes engulfed by mice arterial endothelial cells (MAEC). The role of STC-1-ADSC-Exosome (S-ADSC-Exo) in MAECs was verified through scratch test and tube forming. Expressions of STC-1 and NLRP3 inflammasome were detected by western blot and quantitative reverse transcription polymerase chain reaction. Reendothelialization effect was inhibited by the antagonist of siRNA targeting STC-1. Carotid endarterium mechanical injury was induced by insertion with a guidewire into the common carotid artery lumen. Carotid arteries were harvested for histological examination, immunofluorescence staining, and Evan's blue staining. RESULTS Transfection of STC-1 significantly enhanced STC-1 levels in ADSCs, their exosomes, and MAECs. Compared with the control group and the ADSC-Exo group, STC-1 enriched exosomes markedly inhibited the expressions of NLRP3, Caspase-1, and IL-1β in MAECs, exhibited good lateral migration capacity, and promoted angiogenesis. Administration of siRNA targeting STC-1 completely abolished down-regulation of NLRP3, Caspase-1, and IL-1β by STC-1 and inhibited effects of S-ADSC-Exo on lateral migration and angiogenesis. In vivo administration of S-ADSC-Exo had reendothelialization effect on post-injury carotid endarterium as evidenced by thinner arterial wall, low-expressed NLRP3 inflammasome, and more living endothelial cells. CONCLUSIONS The reendothelialization effect of exosomes from ADSCs on post-injury carotid endarterium could be enhanced by genetic modification of the exosomes to contain elevated STC-1, possibly through suppression of NLRP3 inflammasome-mediated inflammation.
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A randomized, controlled clinical trial of autologous stromal vascular fraction cells transplantation to promote mechanical stretch-induced skin regeneration. Stem Cell Res Ther 2021; 12:243. [PMID: 33858504 PMCID: PMC8048343 DOI: 10.1186/s13287-021-02318-5] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2020] [Accepted: 03/30/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND The regeneration response of the skin to mechanical stretching in vivo has been explored in reconstructive surgery to repair large-scale deformities. The ability of the skin to regenerate limits the reconstructive outcome. Here, we propose an approach in which autologous stromal vascular fraction (SVF) cells and mechanical stretching are combined to overcome this limitation and promote skin regeneration. METHODS This randomized, blinded, placebo-controlled clinical trial screened 22 participants undergoing tissue expansion with exhausted regeneration. Twenty eligible participants received intradermal injections of the SVF or placebo treatments. Follow-ups were conducted at 4, 8, and 12 weeks to assess efficacy and at 2 years to assess safety. The primary endpoint was the expanded skin thickness at 12 weeks. The secondary endpoints included skin thickness at 4 and 8 weeks, the expansion index (EI), and the skin texture score at 12 weeks. RESULTS The skin thickness of the SVF group was significantly higher than that of the control group at both 8 weeks (mean difference 0.78 [95% CI - 1.43 to - 0.11]; p = 0.018) and 12 weeks (0.65 [95% CI - 1.30 to - 0.01]; p = 0.046). In the SVF group, the increase in skin thickness was significant at 4 weeks (0.49 [95% CI - 0.80 to - 0.06]; p = 0.010) to 8 weeks (0.45 [95% CI - 0.92 to 0.02]; p = 0.026) and maintained after 12 weeks, whereas that in the control group was reduced after 8 weeks (0.42 [95% CI - 0.07 to 0.91]; p = 0.037). The SVF group showed greater EI increases than the control group (0.50 [95% CI - 0.00 to 0.99]; p = 0.047). The skin texture scores in the SVF group were greater than those in the control group at 12 weeks. Histologically, SVF-treated expanded skin showed more proliferating cells and blood vessels, and the extracellular matrix volume increased. No severe adverse events occurred. CONCLUSIONS Transplantation of SVF cells can expedite the potency of mechanical stretch-induced skin regeneration and provide clinical reconstruction with plentiful tissue. TRIAL REGISTRATION This trial was registered with the Chinese Clinical Trial Registry, ChiCTR2000039317 (registered 23 October 2020-retrospectively registered).
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Arcucci V, Stacker SA, Achen MG. Control of Gene Expression by Exosome-Derived Non-Coding RNAs in Cancer Angiogenesis and Lymphangiogenesis. Biomolecules 2021; 11:249. [PMID: 33572413 PMCID: PMC7916238 DOI: 10.3390/biom11020249] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2020] [Revised: 01/29/2021] [Accepted: 02/04/2021] [Indexed: 12/12/2022] Open
Abstract
Abstract: Tumour angiogenesis and lymphangiogenesis are hallmarks of cancer and have been associated with tumour progression, tumour metastasis and poor patient prognosis. Many factors regulate angiogenesis and lymphangiogenesis in cancer including non-coding RNAs which are a category of RNAs that do not encode proteins and have important regulatory functions at transcriptional and post-transcriptional levels. Non-coding RNAs can be encapsulated in extracellular vesicles called exosomes which are secreted by tumour cells or other cells in the tumour microenvironment and can then be taken up by the endothelial cells of blood vessels and lymphatic vessels. The "delivery" of these non-coding RNAs to endothelial cells in tumours can facilitate tumour angiogenesis and lymphangiogenesis. Here we review recent findings about exosomal non-coding RNAs, specifically microRNAs and long non-coding RNAs, which regulate tumour angiogenesis and lymphangiogenesis in cancer. We then focus on the potential use of these molecules as cancer biomarkers and opportunities for exploiting ncRNAs for the treatment of cancer.
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Affiliation(s)
- Valeria Arcucci
- Tumour Angiogenesis and Microenvironment Program, Peter MacCallum Cancer Centre, 305 Grattan St., Melbourne VIC 3000, Australia; (V.A.); (S.A.S.)
- Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville VIC 3010, Australia
| | - Steven A. Stacker
- Tumour Angiogenesis and Microenvironment Program, Peter MacCallum Cancer Centre, 305 Grattan St., Melbourne VIC 3000, Australia; (V.A.); (S.A.S.)
- Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville VIC 3010, Australia
- Department of Surgery, Royal Melbourne Hospital, The University of Melbourne, Parkville VIC 3050, Australia
| | - Marc G. Achen
- O’Brien Institute Department, St Vincent’s Institute of Medical Research, 9 Princes Street, Fitzroy VIC 3065, Australia
- Department of Medicine, St Vincent’s Hospital, University of Melbourne, Fitzroy VIC 3065, Australia
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