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Qiu ZY, Xu WC, Liang ZH. Bone marrow mesenchymal stem cell-derived exosomal miR-221-3p promotes angiogenesis and wound healing in diabetes via the downregulation of forkhead box P1. Diabet Med 2024; 41:e15386. [PMID: 38887963 DOI: 10.1111/dme.15386] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Revised: 05/15/2024] [Accepted: 05/28/2024] [Indexed: 06/20/2024]
Abstract
AIM Impaired wound healing in patients with diabetes can develop into nonhealing ulcerations. Because bone marrow mesenchymal stem cells (BMSCs) exosomes can promote wound healing, this study aims to investigate the mechanism of BMSCs-isolated exosomal miR-221-3p in angiogenesis and diabetic wound healing. METHODS To mimic diabetes in vitro, human umbilical vein endothelial cells (HUVECs) were subjected to high glucose (HG). Exosomes were derived from BMSCs and identified by transmission electron microscopy (TEM), western blot analysis and dynamic light scattering (DLS). The ability to differentiate BMSCs was assessed via Oil red O staining, alkaline phosphatase (ALP) staining and alizarin red staining. The ability to internalise PKH26-labelled exosomes was assessed using confocal microscopy. Migration, cell viability and angiogenesis were tested by scratch, MTT and tube formation assays separately. The miRNA and protein levels were analysed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) or western blotting. The relationship among miR-221-3p, FOXP1 and SPRY1 was determined using the dual-luciferase reporter, ChIP and RIP assays. RESULTS Exosomal miR-221-3p was successfully isolated from BMSCs and delivered into HUVECs. HG was found to suppress the angiogenesis, cell viability and migration of HUVECs and exosomal miR-221-3p separated from BMSCs inhibited the above phenomenon. FOXP1 could transcriptionally upregulate SPRY1, and the silencing of FOXP1 reversed the HG-stimulated angiogenesis inhibition, cell viability and migration in HUVECs via the downregulation of SPRY1. Meanwhile, miR-221-3p directly targeted FOXP1 and the overexpression of FOXP1 reversed the positive effect of exosomal miR-221-3p on HUVEC angiogenesis. CONCLUSION Exosomal miR-221-3p isolated from BMSCs promoted angiogenesis in diabetic wounds through the mediation of the FOXP1/SPRY1 axis. Furthermore, the findings of this study can provide new insights into probing strategies against diabetes.
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Affiliation(s)
- Zhi-Yang Qiu
- Department of Burn &Skin Repair Surgery, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou, Hainan, China
| | - Wei-Cheng Xu
- Department of Burn &Skin Repair Surgery, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou, Hainan, China
| | - Zun-Hong Liang
- Department of Burn &Skin Repair Surgery, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou, Hainan, China
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Wang G, Zheng J, Wu H, Wu Y. Effects of electromagnetic therapy in treating patients with venous leg ulcers: An overview of systematic reviews. Int Wound J 2024; 21:e14852. [PMID: 38584310 PMCID: PMC10999496 DOI: 10.1111/iwj.14852] [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: 01/18/2024] [Revised: 03/09/2024] [Accepted: 03/11/2024] [Indexed: 04/09/2024] Open
Abstract
This study aims to evaluate the effects of electromagnetic therapy (EMT) on the treatment of venous leg ulcers (VLUs) by synthesising and appraising available meta-analyses (MAs) and systematic reviews (SRs). A comprehensive literature search was conducted across major databases up to 10 January 2024, focusing on SRs/MAs that investigated the use of EMT for VLUs. Selection criteria followed the PICO framework, and dual-author extraction was used for accuracy. Quality assessment tools included AMSTAR2, ROBIS, PRISMA, and GRADE. The search yielded five eligible studies. The reviews collectively presented moderate methodological quality and a low risk of bias in several domains. Reporting quality was high, albeit with inconsistencies in fulfilling certain PRISMA checklist items. The evidence quality, primarily downgraded due to small sample sizes, was rated as moderate. Whilst some studies suggest potential benefits of EMT in the treatment of VLUs, the overall evidence is inconclusive due to methodological limitations and limited sample sizes. This review underscores the need for future research with more rigorous methodologies and larger cohorts to provide clearer insights into the efficacy of EMT for VLUs.
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Affiliation(s)
- Guofeng Wang
- Department of Respiratory and Critical Care MedicineThe First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine)HangzhouChina
| | - Jie Zheng
- The First Clinical Medical SchoolGuangzhou University of Chinese MedicineGuangzhouChina
| | - Hongxue Wu
- Department of Respiratory and Critical Care MedicineThe First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine)HangzhouChina
| | - Yucheng Wu
- Department of Respiratory and Critical Care MedicineThe First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine)HangzhouChina
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Wei P, Wu L, Xie H, Chen Z, Tan R, Xu Z. Application of a meshed artificial dermal scaffold and negative-pressure wound therapy in the treatment of full-thickness skin defects: a prospective in vivo study. Biomater Sci 2024; 12:1914-1923. [PMID: 38436071 DOI: 10.1039/d3bm01675g] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/05/2024]
Abstract
Artificial dermal scaffolds (ADSs) have great value in repairing deep skin defects. However, problems such as unsatisfactory angiogenesis and local dropsy or empyema often occur, resulting in delayed or even failed wound healing. Negative pressure wound therapy (NPWT) is an effective therapy to promote wound healing or shorten wound bed preparation time. Studies on whether it can improve the effects of ADSs have never been interrupted, and no consensus has been reached. In this study, an improved ADS was prepared by mesh technology, physicochemical experiments were conducted, cell adhesion and proliferation were assessed with the meshed ADS, and in vivo experiments were conducted to investigate the effects of meshed ADS or ADS combined with NPWT in repairing full-thickness skin defects. The results showed that the meshed ADS showed through-layer channels arranged in parallel longitudinal and transverse intersections. The cell experiments confirmed the good cytocompatibility. The in vivo experiments showed that there were no differences in the take rate or contraction of grafted skin among all experiment groups. The meshed ADS exhibited good histocompatibility, and there were no differences in tissue inflammation, dermal angiogenesis, or degradation among all groups. In addition, necrosis, dropsy, or empyema of the dermal scaffold were found in all experiment groups except for the meshed ADS + NPWT group, which showed better wound repair results, including fewer scaffold-related complications and satisfactory skin graft survival and wound contraction. In conclusion, this novel meshed ADS, which has a regular through-layer mesh structure and possesses stable physicochemical properties and good biocompatibility, combined with NPWT can ensure adequate subdermal drainage and reduce the risk of scaffold-related complications, thereby improving the quality and efficiency of wound repair, promoting a broader application of biomaterials, and helping physicians and readers implement more effective wound management.
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Affiliation(s)
- Pei Wei
- Burn and Wound Repair Department, Fujian Medical University Union Hospital, Fuzhou 350001, China.
- Fujian Burn Institute, Fujian Medical University Union Hospital, Fuzhou 350001, China
- Fujian Provincial Key Laboratory of Burn and Trauma, Fujian Medical University Union Hospital, Fuzhou 350001, China
| | - Lijiao Wu
- Department of Orthopedic Surgery, Fujian Provincial Hospital South Branch, Fuzhou 350001, China
- Shengli Clinical Medical College, Fujian Medical University, Fuzhou 350001, China
| | - Hongteng Xie
- Burn and Wound Repair Department, Fujian Medical University Union Hospital, Fuzhou 350001, China.
- Fujian Burn Institute, Fujian Medical University Union Hospital, Fuzhou 350001, China
- Fujian Provincial Key Laboratory of Burn and Trauma, Fujian Medical University Union Hospital, Fuzhou 350001, China
| | - Zhaohong Chen
- Burn and Wound Repair Department, Fujian Medical University Union Hospital, Fuzhou 350001, China.
- Fujian Burn Institute, Fujian Medical University Union Hospital, Fuzhou 350001, China
- Fujian Provincial Key Laboratory of Burn and Trauma, Fujian Medical University Union Hospital, Fuzhou 350001, China
| | - Rongwei Tan
- GuangDong Engineering Technology Research Center of Implantable Medical Polymer, Shenzhen Lando Biomaterials Co., Ltd., Shenzhen 518107, China
| | - Zhaorong Xu
- Burn and Wound Repair Department, Fujian Medical University Union Hospital, Fuzhou 350001, China.
- Fujian Burn Institute, Fujian Medical University Union Hospital, Fuzhou 350001, China
- Fujian Provincial Key Laboratory of Burn and Trauma, Fujian Medical University Union Hospital, Fuzhou 350001, China
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Kawamoto S, Shinkawa E, Fujiwara S, Oda Y, Jimbo H, Nakano E, Fukumoto T, Ono R, Yasuda T, Minami H. Treatment of dermal ulcer with autologous fibrin glue: Two case reports of an exploratory prospective pilot study. Medicine (Baltimore) 2023; 102:e36134. [PMID: 37986310 PMCID: PMC10659605 DOI: 10.1097/md.0000000000036134] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2023] [Accepted: 10/25/2023] [Indexed: 11/22/2023] Open
Abstract
INTRODUCTION The healing of recurrent and refractory skin ulcers requires a long time, during which there is risk of infection, and hospital admission is occasionally required for surgical or daily conservative treatment. Therefore, the development of promising treatments that promote faster, uneventful healing is a must. Composed of cryoprecipitate and thrombin, fibrin glue has a history of surgical use for preventing bleeding and spinal fluid leakage. Moreover, in-house cryoprecipitates contain higher concentrations of coagulation factors and cytokines that may enhance wound healing than commercially available products. However, the efficacy of completely autologous fibrin glue (AFG) in tissue repair has not yet been fully demonstrated. PATIENT CONCERNS This study aimed to evaluate the efficacy of AFG in the treatment of refractory skin ulcers in comparison with the conventional treatment. DIAGNOSIS Two patients with skin ulcer on their lower extremities due to trauma or scleroderma who showed resistance to conventional treatment were included in the study. Both study participants were diagnosed with refractory skin ulcer and were ineligible for autologous skin transplantation. INTERVENTIONS AFG was prepared following autologous blood donation using a Cryoseal® system. Subsequently, AFG was administered to 50% of the area of each ulcer and observed for 4 weeks in comparison with recombinant basic fibroblast growth factor with bucladesine sodium treatment that was administered to the rest of the ulcer. OUTCOMES The skin ulcer after trauma in participant 1 showed better improvement in the AFG-treated area. Although AFG did not show superiority regarding the ulcer area of a patient with scleroderma, it guarded the continuous exudation from the edge of the swollen skin surrounding the ulcer. CONCLUSION AFG showed effective and beneficial results for wound healing of refractory skin ulcer and prevented exudation without any severe adverse events.
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Affiliation(s)
- Shinichiro Kawamoto
- Department of Transfusion Medicine and Cell Therapy, Kobe University Hospital, Kobe, Hyogo, Japan
- Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Hospital Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Eriko Shinkawa
- Department of Dermatology, Kobe University Hospital, Kobe, Hyogo, Japan
| | - Susumu Fujiwara
- Department of Dermatology, Kobe University Hospital, Kobe, Hyogo, Japan
| | - Yoshiko Oda
- Department of Dermatology, Kobe University Hospital, Kobe, Hyogo, Japan
| | - Haruki Jimbo
- Department of Dermatology, Kobe University Hospital, Kobe, Hyogo, Japan
| | - Eiji Nakano
- Department of Dermatology, Hyogo Cancer Center, Kobe, Hyogo, Japan
| | - Takeshi Fukumoto
- Department of Dermatology, Kobe University Hospital, Kobe, Hyogo, Japan
| | - Ryusuke Ono
- Department of Dermatology, Kobe University Hospital, Kobe, Hyogo, Japan
| | - Takahiro Yasuda
- Division of Medical Devices and Systems, Department of Medical Devices, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
- Device Development Promotion Division, Advanced Medical-Engineering Development Center, Kobe University, Kobe, Hyogo, Japan
| | - Hironobu Minami
- Department of Transfusion Medicine and Cell Therapy, Kobe University Hospital, Kobe, Hyogo, Japan
- Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Hospital Graduate School of Medicine, Kobe, Hyogo, Japan
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Huerta CT, Ortiz YY, Liu ZJ, Velazquez OC. Methods and Limitations of Augmenting Mesenchymal Stem Cells for Therapeutic Applications. Adv Wound Care (New Rochelle) 2023; 12:467-481. [PMID: 36301919 PMCID: PMC10254976 DOI: 10.1089/wound.2022.0107] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Accepted: 09/27/2022] [Indexed: 11/13/2022] Open
Abstract
Significance: Given their capacity for self-renewal, multilineage differentiation, and immunomodulatory potential, mesenchymal stem cells (MSCs) represent a promising modality of clinical therapy for both regenerative medicine and immune diseases. In this study, we review the key approaches and popular methods utilized to boost potency and modify functions of MSCs for clinical purposes as well as their associated limitations. Recent Advances: Several major domains of cell modification strategies are currently employed by investigators to overcome these deficits and augment the therapeutic potential of MSCs. Priming MSCs with soluble factors or pharmacologic agents as well as manipulating oxygen availability in culture have been demonstrated to be effective biochemical methods to augment MSC potential. Distinct genetic and epigenetic methods have emerged in recent years to modify the genetic expression of target proteins and factors thereby modulating MSCs capacity for differentiation, migration, and proliferation. Physical methods utilizing three-dimensional culture methods and alternative cell delivery systems and scaffolds can be used to recapitulate the native MSC niche and augment their engraftment and viability for in vivo models. Critical Issues: Unmodified MSCs have demonstrated only modest benefits in many preclinical and clinical studies due to issues with cell engraftment, viability, heterogeneity, and immunocompatibility between donor and recipient. Furthermore, unmodified MSCs can have low inherent therapeutic potential for which intensive research over the past few decades has been dedicated to improving cell functionality and potency.
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Affiliation(s)
- Carlos Theodore Huerta
- DeWitt Daughtry Family Department of Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Yulexi Y. Ortiz
- DeWitt Daughtry Family Department of Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Zhao-Jun Liu
- DeWitt Daughtry Family Department of Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA
- Vascular Biology Institute, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Omaida C. Velazquez
- DeWitt Daughtry Family Department of Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA
- Vascular Biology Institute, University of Miami Miller School of Medicine, Miami, Florida, USA
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Sun Y, Zhao J, Zhang L, Li Z, Lei S. Effectiveness and safety of stem cell therapy for diabetic foot: a meta-analysis update. Stem Cell Res Ther 2022; 13:416. [PMID: 35964145 PMCID: PMC9375292 DOI: 10.1186/s13287-022-03110-9] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Accepted: 08/02/2022] [Indexed: 01/13/2023] Open
Abstract
BACKGROUND Diabetic foot (DF) is one of the most common and serious complications of diabetes mellitus (DM), which brings great psychological and economic pressure to patients. This study aimed to evaluate the efficacy of stem cells in the treatment of diabetic foot. METHODS All relevant studies in Cochrane, Embase, PubMed, Web of Science, China National Knowledge Infrastructure, and WanFang databases were systematically searched for meta-analysis. The outcomes consisted of ulcer or wound healing rate, amputation rate, new vessels, ankle-brachial index (ABI), transcutaneous oxygen pressure (TcPO2), pain-free walking distance, and rest pain score. Dichotomous outcomes were described as risk ratios (RR) with 95% confidence intervals (CIs), while continuous data were presented as standardized mean differences (SMDs) with 95% CIs. Statistical analysis was performed with RevMan 5.3 software. RESULTS A total of 14 studies with 683 participants were included in the meta-analysis. Meta-analysis showed that stem cell therapy was more effective than conventional therapy in terms of ulcer or wound healing rate [OR = 8.20 (5.33, 12.62)], improvement in lower extremity ischemia(new vessels) [OR = 16.48 (2.88, 94.18)], ABI [MD = 0.13 (0.04, 0.08)], TcO2[MD = 4.23 (1.82, 6.65)], pain-free walking distance [MD = 220.79 (82.10, 359.48)], and rest pain score [MD = - 1.94 (- 2.50, - 1.39)], while the amputation rate was significantly decreased [OR = 0.19 (0.10, 0.36)]. CONCLUSIONS The meta-analysis of the current studies has shown that stem cells are significantly more effective than traditional methods in the treatment of diabetic foot and can improve the quality of life of patients after treatment. Future studies should conduct large-scale, randomized, double-blind, placebo-controlled, multicenter trials with high-quality long-term follow-up to demonstrate the most effective cell types and therapeutic parameters for the treatment of diabetic foot.
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Affiliation(s)
- Yuming Sun
- Department of Plastic and Cosmetic Surgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, Hunan Province, China
| | - Jinhong Zhao
- School of Health Policy and Management, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China
| | - Lifang Zhang
- Department of Plastic and Cosmetic Surgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, Hunan Province, China
| | - Zhexuan Li
- Department of Plastic and Cosmetic Surgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, Hunan Province, China.
| | - Shaorong Lei
- Department of Plastic and Cosmetic Surgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, Hunan Province, China.
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Zhou Y, Zhang XL, Lu ST, Zhang NY, Zhang HJ, Zhang J, Zhang J. Human adipose-derived mesenchymal stem cells-derived exosomes encapsulated in pluronic F127 hydrogel promote wound healing and regeneration. Stem Cell Res Ther 2022; 13:407. [PMID: 35941707 PMCID: PMC9358082 DOI: 10.1186/s13287-022-02980-3] [Citation(s) in RCA: 88] [Impact Index Per Article: 29.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Accepted: 06/21/2022] [Indexed: 11/23/2022] Open
Abstract
Background Large area skin trauma has always been a great challenge for both patients and clinicians. Exosomes originating from human adipose-derived mesenchymal stem cells (hADSCs) have been a novel promising cell-free treatment in cutaneous damage repair. Nevertheless, the low retention rate of exosomes post-transplantation in vivo remains a significant challenge in clinical applications. Herein, we purposed to explore the potential clinical application roles of hADSCs-Exos encapsulated in functional PF-127 hydrogel in wound healing.
Methods hADSCs-Exos were isolated from human hADSCs by ultracentrifugation. An injectable, biocompatible, and thermo-sensitive hydrogel Pluronic F-127 hydrogel was employed to encapsulate allogeneic hADSCs-Exos, and this complex was topically applied to a full-thickness cutaneous wound in mice. On different days post-transplantation, the mice were sacrificed, and the skin tissue was excised for histological and immunohistochemical analysis.
Results Compared with hADSCs-Exos or PF-127 only, PF-127/hADSCs-Exos complexes enhanced skin wound healing, promoted re-epithelialization, increased expression of Ki67, α-SMA, and CD31, facilitated collagen synthesis (Collagen I, Collagen III), up-regulated expression of skin barrier proteins (KRT1, AQP3), and reduced inflammation (IL-6, TNF-α, CD68, CD206). By using PF-127/hADSCs-Exos complexes, hADSCs-Exos can be administrated at lower doses frequency while maintaining the same therapeutic effects. Conclusion Administration of hADSCs-Exos in PF-127 improves the efficiency of exosome delivery, maintains the bioactivity of hADSCs-Exos, and optimizes the performance of hADSCs-Exos. Thus, this biomaterial-based exosome will be a promising treatment approach for the cutaneous rejuvenation of skin wounds.
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Affiliation(s)
- Yang Zhou
- Translational Medical Center for Stem Cell Therapy, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200092, China
| | - Xing-Liao Zhang
- Translational Medical Center for Stem Cell Therapy, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200092, China
| | - Shou-Tao Lu
- Translational Medical Center for Stem Cell Therapy, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200092, China.,National United Engineering Laboratory for Biomedical Material Modification Branden Industrial Park, Dezhou, 251100, Shandong, China
| | - Ning-Yan Zhang
- Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Stem Cell Translational Research Center of Tongji Hospital, School of Life Science and Technology, Tongji University, 389 Xincun Road, Shanghai, 200065, China
| | - Hai-Jun Zhang
- National United Engineering Laboratory for Biomedical Material Modification Branden Industrial Park, Dezhou, 251100, Shandong, China. .,Tenth People's Hospital of Tongji University, Shanghai, China.
| | - Jing Zhang
- Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Stem Cell Translational Research Center of Tongji Hospital, School of Life Science and Technology, Tongji University, 389 Xincun Road, Shanghai, 200065, China. .,Shanghai Institute of Stem Cell Research and Clinical Translation, Shanghai, 200120, China.
| | - Jun Zhang
- Translational Medical Center for Stem Cell Therapy, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200092, China. .,Shanghai Institute of Stem Cell Research and Clinical Translation, Shanghai, 200120, China.
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Bone marrow mesenchymal stem cells facilitate diabetic wound healing through the restoration of epidermal cell autophagy via the HIF-1α/TGF-β1/SMAD pathway. Stem Cell Res Ther 2022; 13:314. [PMID: 35841007 PMCID: PMC9284495 DOI: 10.1186/s13287-022-02996-9] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2022] [Accepted: 04/12/2022] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND The biological activity and regenerative medicine of bone marrow mesenchymal stem cells (BMSCs) have been focal topics in the broad fields of diabetic wound repair. However, the molecular mechanisms are still largely elusive for other cellular processes that are regulated during BMSC treatment. Our previous studies have shown that hypoxia is not only a typical pathological phenomenon of wounds but also exerts a vital regulatory effect on cellular bioactivity. In this study, the beneficial effects of hypoxic BMSCs on the cellular behaviors of epidermal cells and diabetic wound healing were investigated. METHOD The viability and secretion ability of hypoxic BMSCs were detected. The autophagy, proliferation and migration of HaCaT cells cultured with hypoxic BMSCs-derived conditioned medium were assessed by estimating the expression of autophagy-related proteins, MTS, EdU proliferation and scratch assays. And the role of the SMAD signaling pathway during hypoxic BMSC-evoked HaCaT cell autophagy was explored through a series of in vitro gain- and loss-of-function experiments. Finally, the therapeutic effects of hypoxic BMSCs were evaluated using full-thickness cutaneous diabetic wound model. RESULTS First, we demonstrated that hypoxic conditions intensify HIF-1α-mediated TGF-β1 secretion by BMSCs. Then, the further data revealed that BMSC-derived TGF-β1 was responsible for the activation of epidermal cell autophagy, which contributed to the induction of epidermal cell proliferation and migration. Here, the SMAD signaling pathway was identified as downstream of BMSC-derived TGF-β1 to regulate HaCaT cell autophagy. Moreover, the administration of BMSCs to diabetic wounds increased epidermal autophagy and the rate of re-epithelialization, leading to accelerated healing, and these effects were significantly attenuated, accompanied by the downregulation of Smad2 phosphorylation levels due to TGF-β1 interference in BMSCs. CONCLUSION In this report, we present evidence that uncovers a previously unidentified role of hypoxic BMSCs in regulating epidermal cell autophagy. The findings demonstrate that BMSC-based treatment by restoring epidermal cell autophagy could be an attractive therapeutic strategy for diabetic wounds and that the process is mediated by the HIF-1α/TGF-β1/SMAD pathway.
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Nugud A, Alghfeli L, Elmasry M, El-Serafi I, El-Serafi AT. Biomaterials as a Vital Frontier for Stem Cell-Based Tissue Regeneration. Front Cell Dev Biol 2022; 10:713934. [PMID: 35399531 PMCID: PMC8987776 DOI: 10.3389/fcell.2022.713934] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Accepted: 03/11/2022] [Indexed: 01/01/2023] Open
Abstract
Biomaterials and tissue regeneration represent two fields of intense research and rapid advancement. Their combination allowed the utilization of the different characteristics of biomaterials to enhance the expansion of stem cells or their differentiation into various lineages. Furthermore, the use of biomaterials in tissue regeneration would help in the creation of larger tissue constructs that can allow for significant clinical application. Several studies investigated the role of one or more biomaterial on stem cell characteristics or their differentiation potential into a certain target. In order to achieve real advancement in the field of stem cell-based tissue regeneration, a careful analysis of the currently published information is critically needed. This review describes the fundamental description of biomaterials as well as their classification according to their source, bioactivity and different biological effects. The effect of different biomaterials on stem cell expansion and differentiation into the primarily studied lineages was further discussed. In conclusion, biomaterials should be considered as an essential component of stem cell differentiation strategies. An intense investigation is still required. Establishing a consortium of stem cell biologists and biomaterial developers would help in a systematic development of this field.
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Affiliation(s)
- Ahmed Nugud
- Pediatric Department, Aljalila Children Hospital, Dubai, United Arab Emirates
| | - Latifa Alghfeli
- Sharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab Emirates
| | - Moustafa Elmasry
- Department of Biomedical and Clinical Sciences (BKV), Linköping University, Linköping, Sweden
- Department of Hand Surgery and Plastic Surgery and Burns, Linköping University Hospital, Linköping, Sweden
| | - Ibrahim El-Serafi
- Department of Hand Surgery and Plastic Surgery and Burns, Linköping University Hospital, Linköping, Sweden
- Basic Medical Sciences Department, College of Medicine, Ajman University, Ajman, United Arab Emirates
| | - Ahmed T. El-Serafi
- Department of Biomedical and Clinical Sciences (BKV), Linköping University, Linköping, Sweden
- Department of Hand Surgery and Plastic Surgery and Burns, Linköping University Hospital, Linköping, Sweden
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Xie J, Wu W, Zheng L, Lin X, Tai Y, Wang Y, Wang L. Roles of MicroRNA-21 in Skin Wound Healing: A Comprehensive Review. Front Pharmacol 2022; 13:828627. [PMID: 35295323 PMCID: PMC8919367 DOI: 10.3389/fphar.2022.828627] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Accepted: 02/10/2022] [Indexed: 12/12/2022] Open
Abstract
MicroRNA-21 (miR-21), one of the early mammalian miRNAs identified, has been detected to be upregulated in multiple biological processes. Increasing evidence has demonstrated the potential values of miR-21 in cutaneous damage and skin wound healing, but lack of a review article to summarize the current evidence on this issue. Based on this review, relevant studies demonstrated that miR-21 played an essential role in wound healing by constituting a complex network with its targeted genes (i.e., PTEN, RECK. SPRY1/2, NF-κB, and TIMP3) and the cascaded signaling pathways (i.e., MAPK/ERK, PI3K/Akt, Wnt/β-catenin/MMP-7, and TGF-β/Smad7-Smad2/3). The treatment effectiveness developed by miR-21 might be associated with the promotion of the fibroblast differentiation, the improvement of angiogenesis, anti-inflammatory, enhancement of the collagen synthesis, and the re-epithelialization of the wound. Currently, miRNA nanocarrier systems have been developed, supporting the feasibility clinical feasibility of such miR-21-based therapy. After further investigations, miR-21 may serve as a potential therapeutic target for wound healing.
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Affiliation(s)
- Jie Xie
- Department of Emergency Medicine, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, China
| | - Weizhou Wu
- Department of Urology, Maoming People's Hospital, Guangdong, China
| | - Liying Zheng
- Postgraduate Pepartment, First Affiliated Hospital of Gannan Medical College, Ganzhou, China
| | - Xuesong Lin
- Department of Burn Surgery, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, China
| | - Yuncheng Tai
- Department of Burn Surgery, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, China
| | - Yajie Wang
- Department of Burn Surgery, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, China
| | - Le Wang
- Department of Burn Surgery, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, China
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Verboket RD, Söhling N, Heilani M, Fremdling C, Schaible A, Schröder K, Brune JC, Marzi I, Henrich D. The Induced Membrane Technique—The Filling Matters: Evaluation of Different Forms of Membrane Filling with and without Bone Marrow Mononuclear Cells (BMC) in Large Femoral Bone Defects in Rats. Biomedicines 2022; 10:biomedicines10030642. [PMID: 35327444 PMCID: PMC8945121 DOI: 10.3390/biomedicines10030642] [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: 02/09/2022] [Revised: 03/07/2022] [Accepted: 03/08/2022] [Indexed: 12/04/2022] Open
Abstract
The Masquelet technique is used to treat large bone defects; it is a two-stage procedure based on an induced membrane. To improve the induced membrane process, demineralized bone matrix in granular (GDBM) and fibrous form (f-DBM) was tested with and without bone marrow mononuclear cells (BMC) as filling of the membrane against the gold standard filling with syngeneic cancellous bone (SCB). A total of 65 male Sprague–Dawley rats obtained a 5 mm femoral defect. These defects were treated with the induced membrane technique and filled with SCB, GDBM, or f-DBM, with or without BMC. After a healing period of eight weeks, the femurs were harvested and submitted for histological, radiological, and biomechanical analyses. The fracture load in the defect zone was lower compared to SCB in all groups. However, histological analysis showed comparable new bone formation, bone mineral density, and cartilage proportions and vascularization. The results suggest that f-DBM in combination with BMC and the induced membrane technique cannot reproduce the very good results of this material in large, non-membrane coated bone defects, nevertheless it supports the maturation of new bone tissue locally. It can be concluded that BMC should be applied in lower doses and inflammatory cells should be removed from the cell preparation before implantation.
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Affiliation(s)
- René D. Verboket
- Department of Trauma, Hand and Reconstructive Surgery, Goethe University Frankfurt, 60590 Frankfurt am Main, Germany; (N.S.); (M.H.); (C.F.); (A.S.); (I.M.); (D.H.)
- Correspondence: ; Tel.: +49-69-6301-7110
| | - Nicolas Söhling
- Department of Trauma, Hand and Reconstructive Surgery, Goethe University Frankfurt, 60590 Frankfurt am Main, Germany; (N.S.); (M.H.); (C.F.); (A.S.); (I.M.); (D.H.)
| | - Myriam Heilani
- Department of Trauma, Hand and Reconstructive Surgery, Goethe University Frankfurt, 60590 Frankfurt am Main, Germany; (N.S.); (M.H.); (C.F.); (A.S.); (I.M.); (D.H.)
| | - Charlotte Fremdling
- Department of Trauma, Hand and Reconstructive Surgery, Goethe University Frankfurt, 60590 Frankfurt am Main, Germany; (N.S.); (M.H.); (C.F.); (A.S.); (I.M.); (D.H.)
| | - Alexander Schaible
- Department of Trauma, Hand and Reconstructive Surgery, Goethe University Frankfurt, 60590 Frankfurt am Main, Germany; (N.S.); (M.H.); (C.F.); (A.S.); (I.M.); (D.H.)
| | - Katrin Schröder
- Center of Physiology, Cardiovascular Physiology, Goethe University Frankfurt, 60590 Frankfurt am Main, Germany;
| | - Jan C. Brune
- German Institute for Cell and Tissue Replacement (DIZG, gemeinnützige GmbH), 12555 Berlin, Germany;
| | - Ingo Marzi
- Department of Trauma, Hand and Reconstructive Surgery, Goethe University Frankfurt, 60590 Frankfurt am Main, Germany; (N.S.); (M.H.); (C.F.); (A.S.); (I.M.); (D.H.)
| | - Dirk Henrich
- Department of Trauma, Hand and Reconstructive Surgery, Goethe University Frankfurt, 60590 Frankfurt am Main, Germany; (N.S.); (M.H.); (C.F.); (A.S.); (I.M.); (D.H.)
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12
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Engineering injectable vascularized tissues from the bottom-up: Dynamics of in-gel extra-spheroid dermal tissue assembly. Biomaterials 2021; 279:121222. [PMID: 34736148 DOI: 10.1016/j.biomaterials.2021.121222] [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: 06/09/2021] [Revised: 09/30/2021] [Accepted: 10/21/2021] [Indexed: 02/05/2023]
Abstract
Modular tissue engineering approaches open up exciting perspectives for the biofabrication of vascularized tissues from the bottom-up, using micro-sized units such as spheroids as building blocks. While several techniques for 3D spheroid formation from multiple cell types have been reported, strategies to elicit the extra-spheroid assembly of complex vascularized tissues are still scarce. Here we describe an injectable approach to generate vascularized dermal tissue, as an example application, from spheroids combining fibroblasts and endothelial progenitors (OEC) in a xeno-free (XF) setting. Short-term cultured spheroids (1 day) were selected over mature spheroids (7 days), as they showed significantly higher angiogenic sprouting potential. Embedding spheroids in fibrin was crucial for triggering cell migration into the external milieu, while providing a 3D framework for in-gel extra-spheroid morphogenesis. Migrating fibroblasts proliferated and produced endogenous ECM forming a dense tissue, while OEC self-assembled into stable capillaries with lumen and basal lamina. Massive in vitro interconnection between sprouts from neighbouring spheroids rapidly settled an intricate vascular plexus. Upon injection into the chorioallantoic membrane of chick embryos, fibrin-entrapped pre-vascularized XF spheroids developed into a macrotissue with evident host vessel infiltration. After only 4 days, perfused chimeric capillaries with human cells were present in proximal areas, showing fast and functional inosculation between host and donor vessels. This method for generating dense vascularized tissue from injectable building blocks is clinically relevant and potentially useful for a range of applications.
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13
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Gentile P, Garcovich S. Systematic Review: Adipose-Derived Mesenchymal Stem Cells, Platelet-Rich Plasma and Biomaterials as New Regenerative Strategies in Chronic Skin Wounds and Soft Tissue Defects. Int J Mol Sci 2021; 22:1538. [PMID: 33546464 PMCID: PMC7913648 DOI: 10.3390/ijms22041538] [Citation(s) in RCA: 69] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Revised: 01/26/2021] [Accepted: 01/29/2021] [Indexed: 12/14/2022] Open
Abstract
The number of clinical trials evaluating adipose-derived mesenchymal stem cells (AD-MSCs), platelet-rich plasma (PRP), and biomaterials efficacy in regenerative plastic surgery has exponentially increased during the last ten years. AD-MSCs are easily accessible from various fat depots and show intrinsic plasticity in giving rise to cell types involved in wound healing and angiogenesis. AD-MSCs have been used in the treatment of soft tissue defects and chronic wounds, employed in conjunction with a fat grafting technique or with dermal substitute scaffolds and platelet-rich plasma. In this systematic review, an overview of the current knowledge on this topic has been provided, based on existing studies and the authors' experience. A multistep search of the PubMed, MEDLINE, Embase, PreMEDLINE, Ebase, CINAHL, PsycINFO, Clinicaltrials.gov, Scopus database, and Cochrane databases has been performed to identify papers on AD-MSCs, PRP, and biomaterials used in soft tissue defects and chronic wounds. Of the 2136 articles initially identified, 422 articles focusing on regenerative strategies in wound healing were selected and, consequently, only 278 articles apparently related to AD-MSC, PRP, and biomaterials were initially assessed for eligibility. Of these, 85 articles were excluded as pre-clinical, experimental, and in vitro studies. For the above-mentioned reasons, 193 articles were selected; of this amount, 121 letters, expert opinions, commentary, and editorials were removed. The remaining 72 articles, strictly regarding the use of AD-MSCs, PRP, and biomaterials in chronic skin wounds and soft tissue defects, were analyzed. The studies included had to match predetermined criteria according to the patients, intervention, comparator, outcomes, and study design (PICOS) approach. The information analyzed highlights the safety and efficacy of AD-MSCs, PRP, and biomaterials on soft tissue defects and chronic wounds, without major side effects.
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Affiliation(s)
- Pietro Gentile
- Department of Surgical Science, Plastic and Reconstructive Surgery, “Tor Vergata” University, 00133 Rome, Italy
- Scientific Director of Academy of International Regenerative Medicine & Surgery Societies (AIRMESS), 1201 Geneva, Switzerland
| | - Simone Garcovich
- Institute of Dermatology, F. Policlinico Gemelli IRCSS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy;
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14
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De Angelis B, Gentile P. Reply to: Observation on the article "Long-term follow-up comparison of two different bilayer dermal substitutes in tissue regeneration: Clinical outcomes and histological findings". Int Wound J 2020; 17:1738-1739. [PMID: 32592223 PMCID: PMC7948772 DOI: 10.1111/iwj.13383] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2020] [Accepted: 04/13/2020] [Indexed: 11/30/2022] Open
Affiliation(s)
| | - Pietro Gentile
- Department of Surgical ScienceUniversity of Rome Tor VergataRomeItaly
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15
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Ren SY, Liu YS, Zhu GJ, Liu M, Shi SH, Ren XD, Hao YG, Gao RD. Strategies and challenges in the treatment of chronic venous leg ulcers. World J Clin Cases 2020; 8:5070-5085. [PMID: 33269244 DOI: 10.12998/wjcc.v8.i21.5070.pmid:] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2020] [Revised: 08/06/2020] [Accepted: 09/28/2020] [Indexed: 02/05/2023] Open
Abstract
Evaluating patients with chronic venous leg ulcers (CVLUs) is essential to find the underlying etiology. The basic tenets in managing CVLUs are to remove the etiological causes, to address systemic and metabolic conditions, to examine the ulcers and artery pulses, and to control wound infection with debridement and eliminating excessive pressure on the wound. The first-line treatments of CVLUs remain wound care, debridement, bed rest with leg elevation, and compression. Evidence to support the efficacy of silver-based dressings in healing CVLUs is unavailable. Hydrogen peroxide is harmful to the growth of granulation tissue in the wound. Surgery options include a high ligation with or without stripping or ablation of the GSVs depending on venous reflux or insufficiency. Yet, not all CVLUs are candidates for surgical treatment because of comorbidities. When standard care of wound for 4 wk failed to heal CVLUs effectively, use of advanced wound care should be considered based on the available evidence. Negative pressure wound therapy facilitates granulation tissue development, thereby helping closure of CVLUs. Autologous split-thickness skin grafting is still the gold standard approach to close huge CVLUs. Hair punch graft appears to have a better result than traditional hairless punch graft for CVLUs. Application of adipose tissue or placenta-derived mesenchymal stem cells is a promising therapy for wound healing. Autologous platelet-rich plasma provides an alternative strategy for surgery for safe and natural healing of the ulcer. The confirmative efficacy of current advanced ulcer therapies needs more robust evidence.
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Affiliation(s)
- Shi-Yan Ren
- Department of General Surgery and Vascular Surgery, Aviation General Hospital, China Medical University, Beijing 100012, China.
| | - Yong-Sheng Liu
- Department of Dermatology, Aviation General Hospital, Beijing 100012, China
| | - Guo-Jian Zhu
- Department of General Surgery, Taian Communications Hospital, Taian 271000, Shandong Province, China
| | - Meng Liu
- Department of Surgery, Tianjin Hexi Hospital, Tianjin 300202, Tianjin, China
| | - Shao-Hui Shi
- Department of Orthopaedic Surgery, Aviation General Hospital, China Medical University, Beijing 100012, China
| | - Xiao-Dong Ren
- Department of Surgery, Wanquanqu Zhongyi Hospital, Zhangjiakou 076250, Hebei Province, China
| | - Ya-Guang Hao
- Department of Medical Administrative, Aviation General Hospital, China Medical University, Beijing 100012, China
| | - Rong-Ding Gao
- Department of General Surgery, Aviation General Hospital, China Medical University, Beijing 100012, China
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16
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Ren SY, Liu YS, Zhu GJ, Liu M, Shi SH, Ren XD, Hao YG, Gao RD. Strategies and challenges in the treatment of chronic venous leg ulcers. World J Clin Cases 2020; 8:5070-5085. [PMID: 33269244 PMCID: PMC7674718 DOI: 10.12998/wjcc.v8.i21.5070] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2020] [Revised: 08/06/2020] [Accepted: 09/28/2020] [Indexed: 02/05/2023] Open
Abstract
Evaluating patients with chronic venous leg ulcers (CVLUs) is essential to find the underlying etiology. The basic tenets in managing CVLUs are to remove the etiological causes, to address systemic and metabolic conditions, to examine the ulcers and artery pulses, and to control wound infection with debridement and eliminating excessive pressure on the wound. The first-line treatments of CVLUs remain wound care, debridement, bed rest with leg elevation, and compression. Evidence to support the efficacy of silver-based dressings in healing CVLUs is unavailable. Hydrogen peroxide is harmful to the growth of granulation tissue in the wound. Surgery options include a high ligation with or without stripping or ablation of the GSVs depending on venous reflux or insufficiency. Yet, not all CVLUs are candidates for surgical treatment because of comorbidities. When standard care of wound for 4 wk failed to heal CVLUs effectively, use of advanced wound care should be considered based on the available evidence. Negative pressure wound therapy facilitates granulation tissue development, thereby helping closure of CVLUs. Autologous split-thickness skin grafting is still the gold standard approach to close huge CVLUs. Hair punch graft appears to have a better result than traditional hairless punch graft for CVLUs. Application of adipose tissue or placenta-derived mesenchymal stem cells is a promising therapy for wound healing. Autologous platelet-rich plasma provides an alternative strategy for surgery for safe and natural healing of the ulcer. The confirmative efficacy of current advanced ulcer therapies needs more robust evidence.
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Affiliation(s)
- Shi-Yan Ren
- Department of General Surgery and Vascular Surgery, Aviation General Hospital, China Medical University, Beijing 100012, China
| | - Yong-Sheng Liu
- Department of Dermatology, Aviation General Hospital, Beijing 100012, China
| | - Guo-Jian Zhu
- Department of General Surgery, Taian Communications Hospital, Taian 271000, Shandong Province, China
| | - Meng Liu
- Department of Surgery, Tianjin Hexi Hospital, Tianjin 300202, Tianjin, China
| | - Shao-Hui Shi
- Department of Orthopaedic Surgery, Aviation General Hospital, China Medical University, Beijing 100012, China
| | - Xiao-Dong Ren
- Department of Surgery, Wanquanqu Zhongyi Hospital, Zhangjiakou 076250, Hebei Province, China
| | - Ya-Guang Hao
- Department of Medical Administrative, Aviation General Hospital, China Medical University, Beijing 100012, China
| | - Rong-Ding Gao
- Department of General Surgery, Aviation General Hospital, China Medical University, Beijing 100012, China
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17
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Multipotent adult progenitor cells grown under xenobiotic-free conditions support vascularization during wound healing. Stem Cell Res Ther 2020; 11:389. [PMID: 32894199 PMCID: PMC7487685 DOI: 10.1186/s13287-020-01912-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Revised: 08/19/2020] [Accepted: 08/27/2020] [Indexed: 12/12/2022] Open
Abstract
Background Cell therapy has been evaluated pre-clinically and clinically as a means to improve wound vascularization and healing. While translation of this approach to clinical practice ideally requires the availability of clinical grade xenobiotic-free cell preparations, studies proving the pre-clinical efficacy of the latter are mostly lacking. Here, the potential of xenobiotic-free human multipotent adult progenitor cell (XF-hMAPC®) preparations to promote vascularization was evaluated. Methods The potential of XF-hMAPC cells to support blood vessel formation was first scored in an in vivo Matrigel assay in mice. Next, a dose-response study was performed with XF-hMAPC cells in which they were tested for their ability to support vascularization and (epi) dermal healing in a physiologically relevant splinted wound mouse model. Results XF-hMAPC cells supported blood vessel formation in Matrigel by promoting the formation of mature (smooth muscle cell-coated) vessels. Furthermore, XF-hMAPC cells dose-dependently improved wound vascularization associated with increasing wound closure and re-epithelialization, granulation tissue formation, and dermal collagen organization. Conclusions Here, we demonstrated that the administration of clinical-grade XF-hMAPC cells in mice represents an effective approach for improving wound vascularization and healing that is readily applicable for translation in humans.
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Gentile P, Dionisi L, Pizzicannella J, de Angelis B, de Fazio D, Garcovich S. A randomized blinded retrospective study: the combined use of micro-needling technique, low-level laser therapy and autologous non-activated platelet-rich plasma improves hair re-growth in patients with androgenic alopecia. Expert Opin Biol Ther 2020; 20:1099-1109. [PMID: 32678725 DOI: 10.1080/14712598.2020.1797676] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2020] [Accepted: 07/15/2020] [Indexed: 12/18/2022]
Abstract
INTRODUCTION Mini-invasive therapies based on autologous non-activated Platelet-Rich Plasma (ANA-PRP), Low-Level Laser Therapy (LLL-T), and Micro-Needling Technique (MN-T) used in combining for hair re-growth need to be standardized. OBJECTIVES The work aims to show in vivo outcomes resulted from retrospective case-series study in which ANA-PRP + MN-T + LLL-T were used in combined in patients affected by Androgenic alopecia. METHODS 23 patients were treated, of which 13 males were classified in stage I-V by the Norwood-Hamilton scale, and 10 females were classified in stage I-III by the Ludwig scale. Assessment of hair re-growth was evaluated with photography, physician's and patient's global assessment scale, and standardized phototrichograms during a follow-up: T0 - baseline, T1 - 12 weeks, T2 - 23 weeks, T3 - 44 weeks, T4 - 58 weeks. RESULTS Interesting outcomes represented by a hair density increase of 81 ± 5 hairs/cm2 and 57 ± 7 hairs/cm2 respectively at T1 and T2 compared with baseline (173 ± 5 hairs/cm2 at T1 and 149 ± 9 hairs/cm2 at T2 versus 92 ± 2 hairs/cm2 at baseline) were observed using computerized trichograms. EXPERT OPINION The main limitation in the autologous regenerative therapies and biotechnologies in hair-regrowth is the extreme variability of PRP products used, in the absence of standardized protocols and widely shared. Appropriate PRP preparations have to be pick after carefully thinking about their bio-molecular specifications and intended indications for use in patients. This approach will aid in matching the optimal PRP product to specific patient factors, leading to improved outcomes and the elucidation of the cost-effectiveness of this treatment. The combined use of biotechnologies as the association of PRP with micro-needling and low-level laser therapy may improve the results in terms of hair count and hair density compared with those obtained by alone PRP. All the procedures must be performed in the full respect of international and local rules. CONCLUSIONS The effect of the combined use of MN-T, LLL-T, and ANA-PRP has been demonstrated.
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Affiliation(s)
- Pietro Gentile
- Department of Surgical Sciences, Plastic and Reconstructive Surgery, University of Rome "Tor Vergata" School of Medicine , Rome, Italy
| | | | | | - Barbara de Angelis
- Department of Surgical Sciences, Plastic and Reconstructive Surgery, University of Rome "Tor Vergata" School of Medicine , Rome, Italy
| | | | - Simone Garcovich
- Institute of Dermatology, F. Policlinico Gemelli IRCSS, Università Cattolica del Sacro Cuore , Rome, Italy
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De Francesco F, Busato A, Mannucci S, Zingaretti N, Cottone G, Amendola F, De Francesco M, Merigo F, Riccio V, Vaienti L, Parodi PC, Sbarbati A, Riccio M. Artificial dermal substitutes for tissue regeneration: comparison of the clinical outcomes and histological findings of two templates. J Int Med Res 2020; 48:300060520945508. [PMID: 32790486 PMCID: PMC7427157 DOI: 10.1177/0300060520945508] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2019] [Accepted: 07/06/2020] [Indexed: 11/15/2022] Open
Abstract
OBJECTIVE Artificial dermal substitutes (DSs) are fundamental in physiological wound healing to ensure consistent and enduring wound closure and provide a suitable scaffold to repair tissue. We compared the clinical and histological features of two DSs, Pelnac and Integra, in the treatment of traumatic and iatrogenic skin defects. METHODS This prospective observational study involved 71 randomly selected patients from our hospital. Wound healing was analyzed using the Wound Surface Area Assessment, the Vancouver Scar Scale, and a visual analog scale. Histological and immunohistochemical evaluations were also performed. RESULTS At 2 weeks, greater regeneration with respect to proliferation of the epidermis and renewal of the dermis was observed with Pelnac than with Integra. At 4 weeks, the dermis had regenerated with both DSs. Both templates induced renewed collagen and revascularization. Differences in the Vancouver Scar Scale score were statistically significant at 4 weeks and 1 year. Pelnac produced a significant increase in contraction at 2 weeks with increasing effectiveness at 4 weeks. Integra produced a higher percentage reduction in the wound surface area and a shorter healing time than Pelnac for wounds >1.5 cm deep. CONCLUSION Our observational data indicate that both DSs are effective and applicable in different clinical contexts.
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Affiliation(s)
- Francesco De Francesco
- Department of Reconstructive Surgery and Hand Surgery, AOU “Ospedali Riuniti”, Ancona, Italy
- Accademia del Lipofilling, Research and Training Center in Regenerative Surgery, Montelabbate (PU), Italy
| | - Alice Busato
- Department of Neuroscience, Biomedicine and Movement, Human Anatomy and Histology Section, University of Verona, Verona, Italy
| | - Silvia Mannucci
- Department of Neuroscience, Biomedicine and Movement, Human Anatomy and Histology Section, University of Verona, Verona, Italy
| | - Nicola Zingaretti
- Accademia del Lipofilling, Research and Training Center in Regenerative Surgery, Montelabbate (PU), Italy
- Clinic of Plastic and Reconstructive Surgery, Department of Medical Area (DAME), University of Udine, Italy
| | - Giuseppe Cottone
- Department of Plastic and Reconstructive Surgery, IRCCS Policlinico San Donato, University of Milan, Milan, Italy
| | - Francesco Amendola
- Department of Plastic and Reconstructive Surgery, IRCCS Policlinico San Donato, University of Milan, Milan, Italy
| | | | - Flavia Merigo
- Department of Neuroscience, Biomedicine and Movement, Human Anatomy and Histology Section, University of Verona, Verona, Italy
| | - Valentina Riccio
- School of Biosciences and Veterinary Medicine, University of Camerino, Matelica, MC, Italy
| | - Luca Vaienti
- Accademia del Lipofilling, Research and Training Center in Regenerative Surgery, Montelabbate (PU), Italy
- Department of Plastic and Reconstructive Surgery, IRCCS Policlinico San Donato, University of Milan, Milan, Italy
| | - Pier Camillo Parodi
- Accademia del Lipofilling, Research and Training Center in Regenerative Surgery, Montelabbate (PU), Italy
- Clinic of Plastic and Reconstructive Surgery, Department of Medical Area (DAME), University of Udine, Italy
| | - Andrea Sbarbati
- Accademia del Lipofilling, Research and Training Center in Regenerative Surgery, Montelabbate (PU), Italy
- Department of Neuroscience, Biomedicine and Movement, Human Anatomy and Histology Section, University of Verona, Verona, Italy
| | - Michele Riccio
- Department of Reconstructive Surgery and Hand Surgery, AOU “Ospedali Riuniti”, Ancona, Italy
- Accademia del Lipofilling, Research and Training Center in Regenerative Surgery, Montelabbate (PU), Italy
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