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Nasadiuk K, Kolanowski T, Kowalewski C, Wozniak K, Oldak T, Rozwadowska N. Harnessing Mesenchymal Stromal Cells for Advanced Wound Healing: A Comprehensive Review of Mechanisms and Applications. Int J Mol Sci 2024; 26:199. [PMID: 39796055 PMCID: PMC11719717 DOI: 10.3390/ijms26010199] [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: 11/29/2024] [Revised: 12/20/2024] [Accepted: 12/24/2024] [Indexed: 01/13/2025] Open
Abstract
Chronic wounds and injuries remain a substantial healthcare challenge, with significant burdens on patient quality of life and healthcare resources. Mesenchymal stromal cells (MSCs) present an innovative approach to enhance tissue repair and regeneration in the context of wound healing. The intrinsic presence of MSCs in skin tissue, combined with their roles in wound repair, ease of isolation, broad secretory profile, and low immunogenicity, makes them especially promising for treating chronic wounds. This review explores the current landscape of MSC application, focusing on preclinical and clinical data across chronic wounds, diabetic ulcers, burns, non-union bone fractures, lower extremity venous ulcers, pressure ulcers, and genetic skin conditions like epidermolysis bullosa. Special emphasis is given to the mechanisms through which MSCs exert their regenerative effects, underscoring their potential in advancing wound healing therapies and supporting the broader field of regenerative medicine.
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Affiliation(s)
- Khrystyna Nasadiuk
- Research and Development Department, Polski Bank Komórek Macierzystych S.A. (FamiCord Group), 00-867 Warsaw, Poland; (K.N.); (T.K.)
| | - Tomasz Kolanowski
- Research and Development Department, Polski Bank Komórek Macierzystych S.A. (FamiCord Group), 00-867 Warsaw, Poland; (K.N.); (T.K.)
- Institute of Human Genetics, Polish Academy of Sciences, 60-479 Poznan, Poland
| | - Cezary Kowalewski
- Department of Dermatology, National Medical Institute of the Ministry of the Interior and Administration, 02-507 Warsaw, Poland; (C.K.); (K.W.)
| | - Katarzyna Wozniak
- Department of Dermatology, National Medical Institute of the Ministry of the Interior and Administration, 02-507 Warsaw, Poland; (C.K.); (K.W.)
| | - Tomasz Oldak
- Research and Development Department, Polski Bank Komórek Macierzystych S.A. (FamiCord Group), 00-867 Warsaw, Poland; (K.N.); (T.K.)
| | - Natalia Rozwadowska
- Institute of Human Genetics, Polish Academy of Sciences, 60-479 Poznan, Poland
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Das P, Pal D, Roy S, Chaudhuri S, Kesh SS, Basak P, Nandi SK. Unveiling advanced strategies for therapeutic stem cell interventions in severe burn injuries: a comprehensive review. Int J Surg 2024; 110:6382-6401. [PMID: 38869979 PMCID: PMC11487052 DOI: 10.1097/js9.0000000000001812] [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: 02/03/2024] [Accepted: 05/29/2024] [Indexed: 06/15/2024]
Abstract
This comprehensive review explores the complex terrain of stem cell therapies as a potential therapeutic frontier in the healing of complicated burn wounds. Serious tissue damage, impaired healing processes, and possible long-term consequences make burn wounds a complex problem. An in-depth review is required since, despite medical progress, existing methods for treating severe burn wounds have significant limitations. Burn wounds are difficult to heal because they cause extensive tissue damage. The challenges of burn injury-induced tissue regeneration and functional recovery are also the subject of this review. Although there is a lot of promise in current stem cell treatments, there are also some limitations with scalability, finding the best way to transport the cells, and finding consistent results across different types of patients. To shed light on how to improve stem cell interventions to heal severe burn wounds, this review covers various stem cell applications in burn wounds and examines these obstacles. To overcome these obstacles, one solution is to enhance methods of stem cell distribution, modify therapies according to the severity of the burn, and conduct more studies on how stem cell therapy affects individual patients. Novel solutions may also be possible through the combination of cutting-edge technologies like nanotechnology and biotechnology. This review seeks to increase stem cell interventions by analyzing present challenges and suggesting strategic improvements. The goal is to provide a more effective and tailored way to repair serious burn wounds.
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Affiliation(s)
- Pratik Das
- Department of Veterinary Surgery and Radiology, West Bengal University of Animal and Fishery Sciences
- School of Bioscience and Engineering, Jadavpur University
| | - Debajyoti Pal
- Department of Veterinary Surgery and Radiology, West Bengal University of Animal and Fishery Sciences
| | - Sudipta Roy
- Department of Veterinary Surgery and Radiology, West Bengal University of Animal and Fishery Sciences
| | - Shubhamitra Chaudhuri
- Department of Veterinary Clinical Complex, West Bengal University of Animal and Fishery Sciences, Kolkata, India
| | - Shyam S. Kesh
- Department of Veterinary Clinical Complex, West Bengal University of Animal and Fishery Sciences, Kolkata, India
| | - Piyali Basak
- School of Bioscience and Engineering, Jadavpur University
| | - Samit K. Nandi
- Department of Veterinary Surgery and Radiology, West Bengal University of Animal and Fishery Sciences
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Xia Y, Wu P, Chen H, Chen Z. Advances in stem cell therapy for diabetic foot. Front Genet 2024; 15:1427205. [PMID: 39290985 PMCID: PMC11405205 DOI: 10.3389/fgene.2024.1427205] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2024] [Accepted: 08/14/2024] [Indexed: 09/19/2024] Open
Abstract
Diabetic Foot Ulcers (DFU) represent a grave complication often encountered in the advanced stages of diabetes mellitus. They frequently lead to recurrent hospitalizations and, in severe cases, can result in life-threatening conditions such as infections, gangrene, and even amputation Diabetic foot ulcers (DFU), as a serious complication in the late stage of diabetes mellitus, are prone to lead to repeated hospitalization, and in severe cases, infection, gangrene, and even amputation. Although there are many methods for treating diabetic foot, there is no clear and effective method to reduce the amputation rate of diabetic foot patients. In recent years, advancements in the understanding of stem cell therapy for the treatment of DFU have shed light on its potential as a novel therapeutic approach. In recent years, as the research on stem cell therapy for diabetic foot is gradually deepening, stem cells are expected to become a new therapeutic method for treating DFU in the future. Their therapeutic effects are through promoting angiogenesis, secreting paracrine factors, controlling inflammation, promoting collagen deposition, and regulating immunity, etc. Despite numerous studies confirming the efficacy of stem cell therapy in treating DFU, there is still a need for the establishment of standardized treatment protocols. Although numerous studies have shown that stem cell therapy for DFU is real and effective, there has not yet been a standardized treatment protocol. This article reviews studies related to stem cell therapy for DFU, looking at the mechanism of action, types of stem cells, and modes of administration.
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Affiliation(s)
- Yinfeng Xia
- Department of Burn and Plastic Surgery, Chongqing University Fuling Hospital, Chongqing University, Chongqing, China
| | - Ping Wu
- Department of Burn and Plastic Surgery, Chongqing University Fuling Hospital, Chongqing University, Chongqing, China
| | - Hong Chen
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing MedicalUniversity, Chongqing, China
| | - Zhiyong Chen
- Department of Burn and Plastic Surgery, Chongqing University Fuling Hospital, Chongqing University, Chongqing, China
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Hetta HF, Elsaghir A, Sijercic VC, Akhtar MS, Gad SA, Moses A, Zeleke MS, Alanazi FE, Ahmed AK, Ramadan YN. Mesenchymal stem cell therapy in diabetic foot ulcer: An updated comprehensive review. Health Sci Rep 2024; 7:e2036. [PMID: 38650719 PMCID: PMC11033295 DOI: 10.1002/hsr2.2036] [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: 11/08/2023] [Revised: 02/06/2024] [Accepted: 03/19/2024] [Indexed: 04/25/2024] Open
Abstract
Background Diabetes has evolved into a worldwide public health issue. One of the most serious complications of diabetes is diabetic foot ulcer (DFU), which frequently creates a significant financial strain on patients and lowers their quality of life. Up until now, there has been no curative therapy for DFU, only symptomatic relief or an interruption in the disease's progression. Recent studies have focused attention on mesenchymal stem cells (MSCs), which provide innovative and potential treatment candidates for several illnesses as they can differentiate into various cell types. They are mostly extracted from the placenta, adipose tissue, umbilical cord (UC), and bone marrow (BM). Regardless of their origin, they show comparable features and small deviations. Our goal is to investigate MSCs' therapeutic effects, application obstacles, and patient benefit strategies for DFU therapy. Methodology A comprehensive search was conducted using specific keywords relating to DFU, MSCs, and connected topics in the databases of Medline, Scopus, Web of Science, and PubMed. The main focus of the selection criteria was on English-language literature that explored the relationship between DFU, MSCs, and related factors. Results and Discussion Numerous studies are being conducted and have demonstrated that MSCs can induce re-epithelialization and angiogenesis, decrease inflammation, contribute to immunological modulation, and subsequently promote DFU healing, making them a promising approach to treating DFU. This review article provides a general snapshot of DFU (including clinical presentation, risk factors and etiopathogenesis, and conventional treatment) and discusses the clinical progress of MSCs in the management of DFU, taking into consideration the side effects and challenges during the application of MSCs and how to overcome these challenges to achieve maximum benefits. Conclusion The incorporation of MSCs in the management of DFU highlights their potential as a feasible therapeutic strategy. Establishing a comprehensive understanding of the complex relationship between DFU pathophysiology, MSC therapies, and related obstacles is essential for optimizing therapy outcomes and maximizing patient benefits.
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Affiliation(s)
- Helal F. Hetta
- Division of Microbiology, Immunology and Biotechnology, Department of Natural Products and Alternative MedicineFaculty of Pharmacy, University of TabukTabukSaudi Arabia
- Department of Medical Microbiology and ImmunologyFaculty of Medicine, Assiut UniversityAssiutEgypt
| | - Alaa Elsaghir
- Department of Microbiology and ImmunologyFaculty of Pharmacy, Assiut UniversityAssiutEgypt
| | | | | | - Sayed A. Gad
- Faculty of Medicine, Assiut UniversityAssiutEgypt
| | | | - Mahlet S. Zeleke
- Menelik II Medical and Health Science College, Kotebe Metropolitan UniversityAddis AbabaEthiopia
| | - Fawaz E. Alanazi
- Department of Pharmacology and ToxicologyFaculty of Pharmacy, University of TabukTabukSaudi Arabia
| | | | - Yasmin N. Ramadan
- Department of Microbiology and ImmunologyFaculty of Pharmacy, Assiut UniversityAssiutEgypt
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Farabi B, Roster K, Hirani R, Tepper K, Atak MF, Safai B. The Efficacy of Stem Cells in Wound Healing: A Systematic Review. Int J Mol Sci 2024; 25:3006. [PMID: 38474251 PMCID: PMC10931571 DOI: 10.3390/ijms25053006] [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: 01/14/2024] [Revised: 02/18/2024] [Accepted: 02/29/2024] [Indexed: 03/14/2024] Open
Abstract
Wound healing is an intricate process involving coordinated interactions among inflammatory cells, skin fibroblasts, keratinocytes, and endothelial cells. Successful tissue repair hinges on controlled inflammation, angiogenesis, and remodeling facilitated by the exchange of cytokines and growth factors. Comorbid conditions can disrupt this process, leading to significant morbidity and mortality. Stem cell therapy has emerged as a promising strategy for enhancing wound healing, utilizing cells from diverse sources such as endothelial progenitor cells, bone marrow, adipose tissue, dermal, and inducible pluripotent stem cells. In this systematic review, we comprehensively investigated stem cell therapies in chronic wounds, summarizing the clinical, translational, and primary literature. A systematic search across PubMed, Embase, Web of Science, Google Scholar, and Cochrane Library yielded 22,454 articles, reduced to 44 studies after rigorous screening. Notably, adipose tissue-derived mesenchymal stem cells (AD-MSCs) emerged as an optimal choice due to their abundant supply, easy isolation, ex vivo proliferative capacities, and pro-angiogenic factor secretion. AD-MSCs have shown efficacy in various conditions, including peripheral arterial disease, diabetic wounds, hypertensive ulcers, bullous diabeticorum, venous ulcers, and post-Mohs micrographic surgery wounds. Delivery methods varied, encompassing topical application, scaffold incorporation, combination with plasma-rich proteins, and atelocollagen administration. Integration with local wound care practices resulted in reduced pain, shorter healing times, and improved cosmesis. Stem cell transplantation represents a potential therapeutic avenue, as transplanted stem cells not only differentiate into diverse skin cell types but also release essential cytokines and growth factors, fostering increased angiogenesis. This approach holds promise for intractable wounds, particularly chronic lower-leg wounds, and as a post-Mohs micrographic surgery intervention for healing defects through secondary intention. The potential reduction in healthcare costs and enhancement of patient quality of life further underscore the attractiveness of stem cell applications in wound care. This systematic review explores the clinical utilization of stem cells and stem cell products, providing valuable insights into their role as ancillary methods in treating chronic wounds.
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Affiliation(s)
- Banu Farabi
- Department of Dermatology, New York Medical College, Valhalla, NY 10595, USA;
- Department of Dermatology, NYC H+Health Hospitals/Metropolitan Hospital Center, New York, NY 10029, USA
- Department of Dermatology, NYC H+Health Hospitals/South Brooklyn Health, Brooklyn, NY 11235, USA
| | - Katie Roster
- School of Medicine, New York Medical College, Valhalla, NY 10595, USA; (K.R.); (R.H.)
| | - Rahim Hirani
- School of Medicine, New York Medical College, Valhalla, NY 10595, USA; (K.R.); (R.H.)
| | - Katharine Tepper
- Phillip Capozzi, M.D. Library, New York Medical College, Valhalla, NY 10595, USA;
| | - Mehmet Fatih Atak
- Department of Internal Medicine, NYC H+Health Hospitals/Metropolitan Hospital Center, New York, NY 10029, USA;
| | - Bijan Safai
- Department of Dermatology, New York Medical College, Valhalla, NY 10595, USA;
- Department of Dermatology, NYC H+Health Hospitals/Metropolitan Hospital Center, New York, NY 10029, USA
- Department of Dermatology, NYC H+Health Hospitals/South Brooklyn Health, Brooklyn, NY 11235, USA
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Shi HS, Yuan X, Wu FF, Li XY, Fan WJ, Yang X, Hu XM, Liu GB. Research progress and challenges in stem cell therapy for diabetic foot: Bibliometric analysis and perspectives. World J Stem Cells 2024; 16:33-53. [PMID: 38292441 PMCID: PMC10824042 DOI: 10.4252/wjsc.v16.i1.33] [Citation(s) in RCA: 1] [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: 09/23/2023] [Revised: 12/06/2023] [Accepted: 12/28/2023] [Indexed: 01/22/2024] Open
Abstract
BACKGROUND Stem cell therapy has shown great potential for treating diabetic foot (DF). AIM To conduct a bibliometric analysis of studies on the use of stem cell therapy for DF over the past two decades, with the aim of depicting the current global research landscape, identifying the most influential research hotspots, and providing insights for future research directions. METHODS We searched the Web of Science Core Collection database for all relevant studies on the use of stem cell therapy in DF. Bibliometric analysis was carried out using CiteSpace, VOSviewer, and R (4.3.1) to identify the most notable studies. RESULTS A search was conducted to identify publications related to the use of stem cells for DF treatment. A total of 542 articles published from 2000 to 2023 were identified. The United States had published the most papers on this subject. In this field, Iran's Shahid Beheshti University Medical Sciences demonstrated the highest productivity. Furthermore, Dr. Bayat from the same university has been an outstanding researcher in this field. Stem Cell Research & Therapy is the journal with the highest number of publications in this field. The main keywords were "diabetic foot ulcers," "wound healing," and "angiogenesis." CONCLUSION This study systematically illustrated the advances in the use of stem cell therapy to treat DF over the past 23 years. Current research findings suggested that the hotspots in this field include stem cell dressings, exosomes, wound healing, and adipose-derived stem cells. Future research should also focus on the clinical translation of stem cell therapies for DF.
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Affiliation(s)
- Hong-Shuo Shi
- Department of Peripheral Vascular Surgery, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 250021, China
| | - Xin Yuan
- Department of Peripheral Vascular Surgery, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 250021, China
| | - Fang-Fang Wu
- Department of Peripheral Vascular Surgery, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 250021, China
| | - Xiao-Yu Li
- Department of Peripheral Vascular Surgery, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 250021, China
| | - Wei-Jing Fan
- Department of Peripheral Vascular Surgery, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 250021, China
| | - Xiao Yang
- Department of Peripheral Vascular Surgery, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 250021, China
| | - Xiao-Ming Hu
- Department of Peripheral Vascular Surgery, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 250021, China
| | - Guo-Bin Liu
- Department of Peripheral Vascular Surgery, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 250021, China.
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Ozhava D, Bektas C, Lee K, Jackson A, Mao Y. Human Mesenchymal Stem Cells on Size-Sorted Gelatin Hydrogel Microparticles Show Enhanced In Vitro Wound Healing Activities. Gels 2024; 10:97. [PMID: 38391427 PMCID: PMC10887759 DOI: 10.3390/gels10020097] [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: 12/22/2023] [Revised: 01/17/2024] [Accepted: 01/22/2024] [Indexed: 02/24/2024] Open
Abstract
The demand for innovative therapeutic interventions to expedite wound healing, particularly in vulnerable populations such as aging and diabetic patients, has prompted the exploration of novel strategies. Mesenchymal stem cell (MSC)-based therapy emerges as a promising avenue for treating acute and chronic wounds. However, its clinical application faces persistent challenges, notably the low survivability and limited retention time of engraftment in wound environments. Addressing this, a strategy to sustain the viability and functionality of human MSCs (hMSCs) in a graft-able format has been identified as crucial for advanced wound care. Hydrogel microparticles (HMPs) emerge as promising entities in the field of wound healing, showcasing versatile capabilities in delivering both cells and bioactive molecules/drugs. In this study, gelatin HMPs (GelMPs) were synthesized via an optimized mild processing method. GelMPs with distinct diameter sizes were sorted and characterized. The growth of hMSCs on GelMPs with various sizes was evaluated. The release of wound healing promoting factors from hMSCs cultured on different GelMPs were assessed using scratch wound assays and gene expression analysis. GelMPs with a size smaller than 100 microns supported better cell growth and cell migration compared to larger sizes (100 microns or 200 microns). While encapsulation of hMSCs in hydrogels has been a common route for delivering viable hMSCs, we hypothesized that hMSCs cultured on GelMPs are more robust than those encapsulated in hydrogels. To test this hypothesis, hMSCs were cultured on GelMPs or in the cross-linked methacrylated gelatin hydrogel (GelMA). Comparative analysis of growth and wound healing effects revealed that hMSCs cultured on GelMPs exhibited higher viability and released more wound healing activities in vitro. This observation highlights the potential of GelMPs, especially those with a size smaller than 100 microns, as a promising carrier for delivering hMSCs in wound healing applications, providing valuable insights for the optimization of advanced therapeutic strategies.
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Affiliation(s)
- Derya Ozhava
- Laboratory for Biomaterials Research, Department of Chemistry and Chemical Biology, Rutgers University, 145 Bevier Rd., Piscataway, NJ 08854, USA
- Department of Chemistry and Chemical Processing Technologies, Cumra Vocational School, Selcuk University, 42130 Konya, Turkey
| | - Cemile Bektas
- Laboratory for Biomaterials Research, Department of Chemistry and Chemical Biology, Rutgers University, 145 Bevier Rd., Piscataway, NJ 08854, USA
| | - Kathleen Lee
- Laboratory for Biomaterials Research, Department of Chemistry and Chemical Biology, Rutgers University, 145 Bevier Rd., Piscataway, NJ 08854, USA
| | - Anisha Jackson
- Laboratory for Biomaterials Research, Department of Chemistry and Chemical Biology, Rutgers University, 145 Bevier Rd., Piscataway, NJ 08854, USA
| | - Yong Mao
- Laboratory for Biomaterials Research, Department of Chemistry and Chemical Biology, Rutgers University, 145 Bevier Rd., Piscataway, NJ 08854, USA
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Mills SJ, Kirby GT, Hofma BR, Smith LE, Statham P, Vaes B, Ting AE, Short R, Cowin AJ. Delivery of multipotent adult progenitor cells via a functionalized plasma polymerized surface accelerates healing of murine diabetic wounds. Front Bioeng Biotechnol 2023; 11:1213021. [PMID: 37675407 PMCID: PMC10477914 DOI: 10.3389/fbioe.2023.1213021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Accepted: 08/09/2023] [Indexed: 09/08/2023] Open
Abstract
Introduction: Stem cell therapies have been investigated as potential treatment modalities for chronic wounds however there has been limited success to date. Multipotent Adult Progenitor Cells (MAPCs©) have been identified as having potential as an allogenic stem cell product due to their high population doubling number and their characteristic dampening of T-cell proliferation. This helps to prevent autoimmunity and graft/cell rejection. Methods: We have developed a dressing, consisting of medical grade silicone coated with a heptylamine plasma polymer, which supports the growth and transfer of MAPCs to skin. To determine if the dressing can deliver functional stem cells into diabetic wounds, they were loaded with MAPCs and then placed over excisional wounds in both normal and diabetic mice. Results and discussion: Accelerated healing was observed in both the normal and diabetic wounds with wound gape being significantly smaller at day 3 when compared to controls. Wound analysis showed that treatment with the MAPC dressings dampened the inflammatory response with reduced numbers of neutrophils and macrophages observed. Additionally, an increase in pro-angiogenic VEGF and CD31 positive endothelial cells was observed indicating improved new blood vessel formation. The MAPC dressings had no effect on fibrosis with collagen I and III being equally affected in both control and treated wounds. Overall, the functionalized MAPC dressings improve healing responses particularly in diabetic mice with impaired healing responses and therefore, show potential for development as an advanced therapeutic approach for the treatment of chronic diabetic wounds.
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Affiliation(s)
- S. J. Mills
- Future Industries Institute, University of South Australia, Mawson Lakes, SA, Australia
- Cooperative Research Centre for Cell Therapy Manufacturing, Adelaide, SA, Australia
| | - G. T. Kirby
- Future Industries Institute, University of South Australia, Mawson Lakes, SA, Australia
- Cooperative Research Centre for Cell Therapy Manufacturing, Adelaide, SA, Australia
| | - B. R. Hofma
- Future Industries Institute, University of South Australia, Mawson Lakes, SA, Australia
- Cooperative Research Centre for Cell Therapy Manufacturing, Adelaide, SA, Australia
| | - L. E. Smith
- Future Industries Institute, University of South Australia, Mawson Lakes, SA, Australia
- Cooperative Research Centre for Cell Therapy Manufacturing, Adelaide, SA, Australia
| | - P. Statham
- Future Industries Institute, University of South Australia, Mawson Lakes, SA, Australia
- Cooperative Research Centre for Cell Therapy Manufacturing, Adelaide, SA, Australia
| | - B. Vaes
- ReGenesys BV, Bio-Incubator Leuven, Leuven, Belgium
| | - A. E. Ting
- Athersys Inc., Cleveland, OH, United States
| | - R. Short
- Material Science Institute, Lancaster University, Lancaster, United Kingdom
| | - A. J. Cowin
- Future Industries Institute, University of South Australia, Mawson Lakes, SA, Australia
- Cooperative Research Centre for Cell Therapy Manufacturing, Adelaide, SA, Australia
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Hu D, Li X, Li J, Tong P, Li Z, Lin G, Sun Y, Wang J. The preclinical and clinical progress of cell sheet engineering in regenerative medicine. Stem Cell Res Ther 2023; 14:112. [PMID: 37106373 PMCID: PMC10136407 DOI: 10.1186/s13287-023-03340-5] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Accepted: 04/13/2023] [Indexed: 04/29/2023] Open
Abstract
Cell therapy is an accessible method for curing damaged organs or tissues. Yet, this approach is limited by the delivery efficiency of cell suspension injection. Over recent years, biological scaffolds have emerged as carriers of delivering therapeutic cells to the target sites. Although they can be regarded as revolutionary research output and promote the development of tissue engineering, the defect of biological scaffolds in repairing cell-dense tissues is apparent. Cell sheet engineering (CSE) is a novel technique that supports enzyme-free cell detachment in the shape of a sheet-like structure. Compared with the traditional method of enzymatic digestion, products harvested by this technique retain extracellular matrix (ECM) secreted by cells as well as cell-matrix and intercellular junctions established during in vitro culture. Herein, we discussed the current status and recent progress of CSE in basic research and clinical application by reviewing relevant articles that have been published, hoping to provide a reference for the development of CSE in the field of stem cells and regenerative medicine.
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Affiliation(s)
- Danping Hu
- Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, 410008, China
- HANGZHOU CHEXMED TECHNOLOGY CO., LTD, Hangzhou, 310000, China
| | - Xinyu Li
- Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, 410008, China
| | - Jie Li
- Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, 410008, China
| | - Pei Tong
- Hospital of Hunan Guangxiu, Medical College of Hunan Normal University, Hunan Normal University, Changsha, 410008, China
| | - Zhe Li
- Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, 410008, China
| | - Ge Lin
- Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, 410008, China
- National Engineering and Research Center of Human Stem Cells, Changsha, 410008, China
- Key Laboratory of Stem Cells and Reproductive Engineering, Ministry of Health, Changsha, 410008, China
| | - Yi Sun
- Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, 410008, China.
- National Engineering and Research Center of Human Stem Cells, Changsha, 410008, China.
- Key Laboratory of Stem Cells and Reproductive Engineering, Ministry of Health, Changsha, 410008, China.
| | - Juan Wang
- Shanghai Biomass Pharmaceutical Product Evaluation Professional Public Service Platform, Center for Pharmacological Evaluation and Research, China State Institute of Pharmaceutical Industry, Shanghai, 200437, China.
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Hosseini M, Shafiee A. Vascularization of cutaneous wounds by stem cells. PROGRESS IN MOLECULAR BIOLOGY AND TRANSLATIONAL SCIENCE 2023; 199:327-350. [PMID: 37678977 DOI: 10.1016/bs.pmbts.2023.03.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/04/2023]
Abstract
Differentiated skin cells have limited self-renewal capacity; thus, the application of stem/progenitor cells, adult or induced stem cells, has attracted much attention for wound healing applications. Upon skin injury, vascularization, known as a highly dynamic process, occurs with the contribution of cells, the extracellular matrix, and relevant growth factors. Considering the importance of this process in tissue regeneration, several strategies have been proposed to enhance angiogenesis and accelerate wound healing. Previous studies report the effectiveness of stem/progenitor cells in skin wound healing by facilitating the vascularization process. This chapter reviews and highlights some of the key and recent investigations on application of stem/progenitor cells to induce skin revascularization after trauma.
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Affiliation(s)
- Motaharesadat Hosseini
- School of Mechanical, Medical and Process Engineering, Faculty of Engineering, Queensland University of Technology, Brisbane, QLD, Australia; ARC Industrial Transformation Training Centre for Multiscale 3D Imaging, Modelling and Manufacturing (M3D), Queensland University of Technology, Brisbane, QLD, Australia
| | - Abbas Shafiee
- Herston Biofabrication Institute, Metro North Hospital and Health Service, Brisbane, QLD, Australia; Royal Brisbane and Women's Hospital, Metro North Hospital and Health Service, Brisbane, QLD, Australia; Frazer Institute, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia.
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Dixit K, Bora H, Lakshmi Parimi J, Mukherjee G, Dhara S. Biomaterial mediated immunomodulation: An interplay of material environment interaction for ameliorating wound regeneration. J Biomater Appl 2023; 37:1509-1528. [PMID: 37069479 DOI: 10.1177/08853282231156484] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/24/2023]
Abstract
Chronic wounds are the outcome of an imbalanced inflammatory response caused by sustenance of immune microenvironment. In this context, tissue engineered graft played great role in healing wounds but faced difficulty in scar remodelling, immune rejection and poor vascularization. All the limitations faced are somewhere linked with the immune cells involved in healing. In this consideration, immunomodulatory biomaterials bridge a large gap with the delivery of modulating factors for triggering key inflammatory cells responsible towards interplay in the wound micro-environment. Inherent physico-chemical properties of biomaterials substantially determine the nature of cell-materials interaction thereby facilitating differential cytokine gradient involved in activation or suppression of inflammatory signalling pathways, and followed by surface marker expression. This review aims to systematically describe the interplay of immune cells involved in different phases in the wound microenvironment and biomaterials. Additionally, it also focuses on modulating innate immune cell responses in the context of triggering the halted phase of the wound healing, i.e., inflammatory phase. The various strategies are highlighted for modulation of wound microenvironment towards wound regeneration including stem cells, cytokines, growth factors, vitamins, and anti-inflammatory agents to induce interactive ability of biomaterials with immune cells. The last section focuses on prospective approaches and current potential strategies for wound regeneration. This includes the development of different models to bridge the gap between mouse models and human patients. Emerging new tools to study inflammatory response owing to biomaterials and novel strategies for modulation of monocyte and macrophage behaviour in the wound environment are also discussed.
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Affiliation(s)
- Krishna Dixit
- Biomaterials and Tissue Engineering Laboratory, School of Medical Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur, India
- Immunology and Inflammation Laboratory, School of Medical Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur, India
| | - Hema Bora
- Biomaterials and Tissue Engineering Laboratory, School of Medical Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur, India
| | - Jhansi Lakshmi Parimi
- Biomaterials and Tissue Engineering Laboratory, School of Medical Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur, India
| | - Gayatri Mukherjee
- Immunology and Inflammation Laboratory, School of Medical Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur, India
| | - Santanu Dhara
- Biomaterials and Tissue Engineering Laboratory, School of Medical Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur, India
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12
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Kim J, Kim EH, Lee H, Sung JH, Bang OY. Clinical-Scale Mesenchymal Stem Cell-Derived Extracellular Vesicle Therapy for Wound Healing. Int J Mol Sci 2023; 24:ijms24054273. [PMID: 36901703 PMCID: PMC10001880 DOI: 10.3390/ijms24054273] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2022] [Revised: 02/14/2023] [Accepted: 02/15/2023] [Indexed: 02/24/2023] Open
Abstract
We developed an extracellular vesicle (EV) bioprocessing platform for the scalable production of human Wharton's jelly mesenchymal stem cell (MSC)-derived EVs. The effects of clinical-scale MSC-EV products on wound healing were tested in two different wound models: subcutaneous injection of EVs in a conventional full-thickness rat model and topical application of EVs using a sterile re-absorbable gelatin sponge in the chamber mouse model that was developed to prevent the contraction of wound areas. In vivo efficacy tests showed that treatment with MSC-EVs improved the recovery following wound injury, regardless of the type of wound model or mode of treatment. In vitro mechanistic studies using multiple cell lines involved in wound healing showed that EV therapy contributed to all stages of wound healing, such as anti-inflammation and proliferation/migration of keratinocytes, fibroblasts, and endothelial cells, to enhance wound re-epithelialization, extracellular matrix remodeling, and angiogenesis.
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Affiliation(s)
- Jieun Kim
- Cell and Gene Institute, Samsung Medical Center, Seoul 06351, Republic of Korea
- Translational and Stem Cell Research Laboratory on Stroke, Samsung Medical Center, Seoul 06351, Republic of Korea
| | - Eun Hee Kim
- S&E Bio, Inc., Seoul 05855, Republic of Korea
| | - Hanbee Lee
- Cell and Gene Institute, Samsung Medical Center, Seoul 06351, Republic of Korea
- Translational and Stem Cell Research Laboratory on Stroke, Samsung Medical Center, Seoul 06351, Republic of Korea
| | - Ji Hee Sung
- S&E Bio, Inc., Seoul 05855, Republic of Korea
| | - Oh Young Bang
- Cell and Gene Institute, Samsung Medical Center, Seoul 06351, Republic of Korea
- Translational and Stem Cell Research Laboratory on Stroke, Samsung Medical Center, Seoul 06351, Republic of Korea
- S&E Bio, Inc., Seoul 05855, Republic of Korea
- Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea
- Correspondence:
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13
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Li Q, Wang D, Jiang Z, Li R, Xue T, Lin C, Deng Y, Jin Y, Sun B. Advances of hydrogel combined with stem cells in promoting chronic wound healing. Front Chem 2022; 10:1038839. [PMID: 36518979 PMCID: PMC9742286 DOI: 10.3389/fchem.2022.1038839] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Accepted: 11/07/2022] [Indexed: 08/15/2023] Open
Abstract
Wounds can be divided into two categories, acute and chronic. Acute wounds heal through the normal wound healing process. However, chronic wounds take longer to heal, leading to inflammation, pain, serious complications, and an economic burden of treatment costs. In addition, diabetes and burns are common causes of chronic wounds that are difficult to treat. The rapid and thorough treatment of chronic wounds, including diabetes wounds and burns, represents a significant unmet medical need. Wound dressings play an essential role in chronic wound treatment. Various biomaterials for wound healing have been developed. Among these, hydrogels are widely used as wound care materials due to their good biocompatibility, moisturizing effect, adhesion, and ductility. Wound healing is a complex process influenced by multiple factors and regulatory mechanisms in which stem cells play an important role. With the deepening of stem cell and regenerative medicine research, chronic wound treatment using stem cells has become an important field in medical research. More importantly, the combination of stem cells and stem cell derivatives with hydrogel is an attractive research topic in hydrogel preparation that offers great potential in chronic wound treatment. This review will illustrate the development and application of advanced stem cell therapy-based hydrogels in chronic wound healing, especially in diabetic wounds and burns.
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Affiliation(s)
- Qirong Li
- Department of Hepatobiliary and Pancreas Surgery, China-Japan Union Hospital of Jilin University, Changchun, China
- Laboratory Animal Center, College of Animal Science, Jilin University, Changchun, China
| | - Dongxu Wang
- Laboratory Animal Center, College of Animal Science, Jilin University, Changchun, China
| | - Ziping Jiang
- Department of Hand and Foot Surgery, The First Hospital of Jilin University, Changchun, China
| | - Rong Li
- Laboratory Animal Center, College of Animal Science, Jilin University, Changchun, China
| | - Tianyi Xue
- Laboratory Animal Center, College of Animal Science, Jilin University, Changchun, China
| | - Chao Lin
- School of Grain Science and Technology, Jilin Business and Technology College, Changchun, China
| | - Yongzhi Deng
- School of Pharmacy, Changchun University of Chinese Medicine, Changchun, China
| | - Ye Jin
- School of Pharmacy, Changchun University of Chinese Medicine, Changchun, China
| | - Baozhen Sun
- Department of Hepatobiliary and Pancreas Surgery, China-Japan Union Hospital of Jilin University, Changchun, China
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14
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Hade MD, Suire CN, Mossell J, Suo Z. Extracellular vesicles: Emerging frontiers in wound healing. Med Res Rev 2022; 42:2102-2125. [PMID: 35757979 DOI: 10.1002/med.21918] [Citation(s) in RCA: 64] [Impact Index Per Article: 21.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2021] [Revised: 12/10/2021] [Accepted: 06/07/2022] [Indexed: 12/19/2022]
Abstract
Extracellular vesicles are membranous particles, ranging from 30 nm to 10 µm in diameter, which are released by nearly all cell types to aid in intercellular communication. These complex vesicles carry a multitude of signaling moieties from their cell of origin, such as proteins, lipids, cell surface receptors, enzymes, cytokines, metabolites, and nucleic acids. A growing body of evidence suggests that in addition to delivering cargos into target cells to facilitate intercellular communication, extracellular vesicles may also play roles in such processes as cell differentiation and proliferation, angiogenesis, stress response, and immune signaling. As these vesicles have natural biocompatibility, stability in circulation, low toxicity, and low immunogenicity, and serve as efficient carriers of molecular cargos, these nanoparticles are ideal therapeutic candidates for regenerative medicine. Exploring and identifying the homeostatic functions of extracellular vesicles may facilitate the development of new regenerative therapies. In this review, we summarize the wound healing process, difficulties in stem cell therapies for regenerative medicine, and the applications of mesenchymal stromal cell-derived extracellular vesicles in improving and accelerating the wound healing process.
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Affiliation(s)
- Mangesh D Hade
- Department of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, Florida, USA
| | - Caitlin N Suire
- Department of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, Florida, USA
| | - James Mossell
- Department of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, Florida, USA
| | - Zucai Suo
- Department of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, Florida, USA
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15
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Platelet-rich plasma: a comparative and economical therapy for wound healing and tissue regeneration. Cell Tissue Bank 2022; 24:285-306. [PMID: 36222966 PMCID: PMC9555256 DOI: 10.1007/s10561-022-10039-z] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Accepted: 09/10/2022] [Indexed: 11/17/2022]
Abstract
Rise in the incidences of chronic degenerative diseases with aging makes wound care a socio-economic burden and unceasingly necessitates a novel, economical, and efficient wound healing treatment. Platelets have a crucial role in hemostasis and thrombosis by modulating distinct mechanistic phases of wound healing, such as promoting and stabilizing the clot. Platelet-rich plasma (PRP) contains a high concentration of platelets than naïve plasma and has an autologous origin with no immunogenic adverse reactions. As a consequence, PRP has gained significant attention as a therapeutic to augment the healing process. Since the past few decades, a robust volume of research and clinical trials have been performed to exploit extensive role of PRP in wound healing/tissue regeneration. Despite these rigorous studies and their application in diversified medical fields, efficacy of PRP-based therapies is continuously questioned owing to the paucity of large samplesizes, controlled clinical trials, and standard protocols. This review systematically delineates the process of wound healing and involvement of platelets in tissue repair mechanisms. Additionally, emphasis is laid on PRP, its preparation methods, handling, classification,application in wound healing, and PRP as regenerative therapeutics combined with biomaterials and mesenchymal stem cells (MSCs).
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16
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Bray ER, Kirsner RS, Badiavas EV. Mesenchymal Stem Cell-Derived Extracellular Vesicles as an Advanced Therapy for Chronic Wounds. Cold Spring Harb Perspect Biol 2022; 14:a041227. [PMID: 35817513 PMCID: PMC9524280 DOI: 10.1101/cshperspect.a041227] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
Chronic wounds are a significant challenge for patients, healthcare providers, and healthcare systems. Chronic wounds develop due to a complex interplay between chronic inflammation, tissue hypoxia, and oxidative stress, often occurring in the setting of advancing age. Ideally, new therapeutics should address all the components of chronic wound pathophysiology. Mesenchymal stem cell (MSC) therapies show significant promise to promote healing of chronic wounds. Extracellular vesicles (EVs) secreted by MSCs mediate many of their beneficial effects. We review the evidence demonstrating that MSC-EVs target the processes leading to chronic wounds. Additionally, we discuss how MSCs can be influenced to generate more potent wound healing EVs. Finally, we highlight the current state of EV clinical trials for wound healing and important preclinical studies that will lead to optimal use of MSC-EVs for patient care.
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Affiliation(s)
- Eric R Bray
- Phillip Frost Department of Dermatology and Cutaneous Surgery
- Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, Florida 33136, USA
| | | | - Evangelos V Badiavas
- Phillip Frost Department of Dermatology and Cutaneous Surgery
- Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, Florida 33136, USA
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17
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Hamel KM, Liimatta KQ, Belgodere JA, Bunnell BA, Gimble JM, Martin EC. Adipose-Derived Stromal/Stem Cell Response to Tumors and Wounds: Evaluation of Patient Age. Stem Cells Dev 2022; 31:579-592. [PMID: 35262397 PMCID: PMC9836707 DOI: 10.1089/scd.2021.0280] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Accepted: 03/05/2022] [Indexed: 01/22/2023] Open
Abstract
Tumors were characterized as nonhealing wounds by Virchow in 1858 and Dvorak in 1986. Since then, researchers have analyzed tumors from a new perspective. The parallels between tumorigenesis and physiological wound healing can provide a new framework for developing antitumor therapeutics. One commonality between tumors and wounds is the involvement of the stromal environment, particularly adipose stromal/stem cells (ASCs). ASCs exhibit dual functions, in which they stimulate tumor progression and assist in tissue repair and regeneration. Numerous studies have focused on the role of ASCs in cancer and wound healing, but none to date has linked age, cancer, and wound healing. Furthermore, very few studies have focused on the role of donor-specific characteristics of ASCs, such as age and their role in facilitating ASC behavior in cancer and wound healing. This review article is designed to provide important insights into the impact of donor age on ASC tumor and wound response and their role in facilitating ASC behavior in cancer and wound healing.
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Affiliation(s)
- Katie M. Hamel
- Department of Biological Engineering, Louisiana State University, Baton Rouge, Louisiana, USA
| | - Kara Q. Liimatta
- Department of Biological Engineering, Louisiana State University, Baton Rouge, Louisiana, USA
| | - Jorge A. Belgodere
- Department of Biological Engineering, Louisiana State University, Baton Rouge, Louisiana, USA
| | - Bruce A. Bunnell
- University of North Texas Health Sciences Center, Fort Worth, Texas, USA
| | | | - Elizabeth C. Martin
- Department of Biological Engineering, Louisiana State University, Baton Rouge, Louisiana, USA
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18
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Feldman D. Designing a Biomaterial Approach to Control the Adaptive Response to a Skin Injury. MATERIALS (BASEL, SWITZERLAND) 2022; 15:6366. [PMID: 36143676 PMCID: PMC9503963 DOI: 10.3390/ma15186366] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Revised: 06/03/2022] [Accepted: 09/01/2022] [Indexed: 06/16/2023]
Abstract
The goal of this review is to explain how to design a biomaterial approach to control the adaptive response to injury, with an emphasis on skin wounds. The strategies will be selected based on whether they have a reasonable probability of meeting the desired clinical outcome vs. just comparing the pros and cons of different strategies. To do this, the review will look at the normal adaptive response in adults and why it does not meet the desired clinical outcome in most cases. In addition, the adaptive response will be looked at in cases where it does meet the clinical performance requirements including animals that regenerate and for fetal wound healing. This will lead to how biomaterials can be used to alter the overall adaptive response to allow it to meet the desired clinical outcome. The important message of the review is that you need to use the engineering design process, not the scientific method, to design a clinical treatment. Also, the clinical performance requirements are functional, not structural. The last section will give some specific examples of controlling the adaptive response for two skin injuries: burns and pressure ulcers. For burns, it will cover some preclinical studies used to justify a clinical study as well as discuss the results of a clinical study using this system. For pressure ulcers, it will cover some preclinical studies for two different approaches: electrical stimulation and degradable/regenerative scaffolds. For electrical stimulation, the results of a clinical study will be presented.
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Affiliation(s)
- Dale Feldman
- Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL 35294, USA
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19
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Azaryan E, Karbasi S, Zarban A, Naseri M. Cell-free therapy based on stem cell-derived exosomes: A promising approach for wound healing. Wound Repair Regen 2022; 30:585-594. [PMID: 35927607 DOI: 10.1111/wrr.13043] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Revised: 06/22/2022] [Accepted: 07/15/2022] [Indexed: 11/28/2022]
Abstract
There are several successive and overlapping phases in wound healing as a complex process. By the disruption of each of these phases, chronic non-healing wounds are resultant. Despite the present soothing surgeries, standard wound dressings and topical gels, the wound is often not completely closed. Today, stem cells have attracted a huge deal of attention therapeutically and pharmaceutically considering their unique features. However, they have some restrictions. Moreover, it is hoped to eliminate the limitations of cellular therapies based on their derivatives known as exosomes. Exosomes are extracellular vesicles secreted from cells. They have a diameter of almost 30-150 nm and miRNAs, mRNAs, and proteins that are possibly different from the source cell are included in exosomal contents. Such nanovesicles have a key role in the intercellular communication of pathological and physiological procedures. Exosome-based therapy is a new significant method for wound healing. By exosomes effects, wound management may be improved and a new therapeutic model may be highlighted for cell-free therapies with reduced side effects for the wound repair.
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Affiliation(s)
- Ehsaneh Azaryan
- Student Research Committee, Birjand University of Medical Sciences, Birjand, Iran
- Cellular and Molecular Research Center, Department of Molecular Medicine, Birjand University of Medical Sciences, Birjand, Iran
| | - Samira Karbasi
- Department of Molecular Medicine, School of Medicine, Cardiovascular Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran
| | - Asghar Zarban
- Cardiovascular Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran
- Clinical Biochemistry Department, Faculty of Medicine, Birjand University of Medical Sciences, Birjand, Iran
| | - Mohsen Naseri
- Cellular and Molecular Research Center, Department of Molecular Medicine, Birjand University of Medical Sciences, Birjand, Iran
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20
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El Hage R, Knippschild U, Arnold T, Hinterseher I. Stem Cell-Based Therapy: A Promising Treatment for Diabetic Foot Ulcer. Biomedicines 2022; 10:1507. [PMID: 35884812 PMCID: PMC9312797 DOI: 10.3390/biomedicines10071507] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Revised: 06/17/2022] [Accepted: 06/21/2022] [Indexed: 11/16/2022] Open
Abstract
Diabetic foot ulcer (DFU) is a severe complication of diabetes and a challenging medical condition. Conventional treatments for DFU have not been effective enough to reduce the amputation rates, which urges the need for additional treatment. Stem cell-based therapy for DFU has been investigated over the past years. Its therapeutic effect is through promoting angiogenesis, secreting paracrine factors, stimulating vascular differentiation, suppressing inflammation, improving collagen deposition, and immunomodulation. It is controversial which type and origin of stem cells, and which administration route would be the most optimal for therapy. We reviewed the different types and origins of stem cells and routes of administration used for the treatment of DFU in clinical and preclinical studies. Diabetes leads to the impairment of the stem cells in the diseased patients, which makes it less ideal to use autologous stem cells, and requires looking for a matching donor. Moreover, angioplasty could be complementary to stem cell therapy, and scaffolds have a positive impact on the healing process of DFU by stem cell-based therapy. In short, stem cell-based therapy is promising in the field of regenerative medicine, but more studies are still needed to determine the ideal type of stem cells required in therapy, their safety, proper dosing, and optimal administration route.
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Affiliation(s)
- Racha El Hage
- Department of Vascular Surgery, Universitätsklinikum Ruppin-Brandenburg, Medizinische Hochschule Branderburg Theodor Fontane, Fehrbelliner Str. 38, 16816 Neuruppin, Germany;
| | - Uwe Knippschild
- Department of General and Visceral Surgery, Surgery Center, Ulm University, Albert-Einstein-Allee 23, 89081 Ulm, Germany; (U.K.); (T.A.)
| | - Tobias Arnold
- Department of General and Visceral Surgery, Surgery Center, Ulm University, Albert-Einstein-Allee 23, 89081 Ulm, Germany; (U.K.); (T.A.)
| | - Irene Hinterseher
- Department of Vascular Surgery, Universitätsklinikum Ruppin-Brandenburg, Medizinische Hochschule Branderburg Theodor Fontane, Fehrbelliner Str. 38, 16816 Neuruppin, Germany;
- Berlin Institute of Health, Vascular Surgery Clinic, Charité-Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany
- Fakultät für Gesundheitswissenschaften Brandenburg, Gemeinsame Fakultät der Universität Potsdam, der Medizinischen Hochschule Brandenburg Theodor Fontane und der Brandenburgischen Technischen Universität Cottbus—Senftenberg, Karl-Liebknecht-Str. 24-25, 14476 Potsdam, Germany
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21
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Tabibzadeh S. Repair, regeneration and rejuvenation require un-entangling pluripotency from senescence. Ageing Res Rev 2022; 80:101663. [PMID: 35690382 DOI: 10.1016/j.arr.2022.101663] [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: 03/07/2022] [Revised: 05/27/2022] [Accepted: 06/04/2022] [Indexed: 11/16/2022]
Abstract
There is a notion that pluripotency and senescence, represent two extremes of life of cells. Pluripotent cells display epigenetic youth, unlimited proliferative capacity and pluripotent differentiating potential whereas cells that reach the Hayflick limit, transit to senescence, undergo permanent inhibition of cell replication and create an aging tissue landscape. However, pluripotency and senescence appear to be intimately linked and are jointly generated in many different contexts such as during embryogenesis or formation of tissue spheroids, in stem cell niches, cancer, or by induction of a pluripotent state (induced pluripotency). Tissue damage and senescence provide signals that are critical to generation of a pluripotent state and, in turn, pluripotency, induces senescence. Thus, it follows, that precisely timed control of senescence is required for harnessing the full benefits of both senescence and its associated pluripotency during tissue regeneration or rejuvenation.
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Affiliation(s)
- Siamak Tabibzadeh
- Frontiers in Bioscience Research Institute in Aging and Cancer, 16471 Scientific Way, Irvine, CA 92618.
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22
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Gopalakrishnan Usha P, Jalajakumari S, Babukuttan Sheela U, Mohan D, Meena Gopalakrishnan A, Sreeranganathan M, Kuttan Pillai R, Berry C, Maiti KK, Therakathinal Thankappan S. Porous polysaccharide scaffolds: Proof of concept study on wound healing and stem cell differentiation. J BIOACT COMPAT POL 2022. [DOI: 10.1177/08839115211073156] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
The combination of desirable polymer properties and methods for synthesis, utilizing materials with various architectures, could be adopted for diverse clinical applications such as wound healing as well as stem cell differentiation. Natural polymers, particularly polysaccharides, are biocompatible and are reported to have structural similarities with extracellular matrix components. In this scenario, the present study fabricated a porous scaffold using a polysaccharide, galactoxyloglucan, isolated from Tamarind seed kernel, and studied its applications in stem cell attachment and wound healing. In-growth of human mesenchymal stem cells (hMSCs) presented a rounded morphology with increased proliferation. Scaffolds were surface-functionalized with silver nanoparticles to increase the antibacterial activity and the wound healing potential evaluated in preclinical mouse models. The current study provides an insight into how stem cells attach and grow in a naturally derived low-cost polysaccharide scaffold with antibacterial, biocompatible, and biodegradable properties.
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Affiliation(s)
- Preethi Gopalakrishnan Usha
- Laboratory of Biopharmaceuticals and Nanomedicine, Division of Cancer Research, Regional Cancer Centre, Thiruvananthapuram, India (Research Centre, University of Kerala)
| | - Sreekutty Jalajakumari
- Laboratory of Biopharmaceuticals and Nanomedicine, Division of Cancer Research, Regional Cancer Centre, Thiruvananthapuram, India (Research Centre, University of Kerala)
| | - Unnikrishnan Babukuttan Sheela
- Laboratory of Biopharmaceuticals and Nanomedicine, Division of Cancer Research, Regional Cancer Centre, Thiruvananthapuram, India (Research Centre, University of Kerala)
| | - Deepa Mohan
- Laboratory of Biopharmaceuticals and Nanomedicine, Division of Cancer Research, Regional Cancer Centre, Thiruvananthapuram, India (Research Centre, University of Kerala)
| | - Archana Meena Gopalakrishnan
- Laboratory of Biopharmaceuticals and Nanomedicine, Division of Cancer Research, Regional Cancer Centre, Thiruvananthapuram, India (Research Centre, University of Kerala)
| | - Maya Sreeranganathan
- Laboratory of Biopharmaceuticals and Nanomedicine, Division of Cancer Research, Regional Cancer Centre, Thiruvananthapuram, India (Research Centre, University of Kerala)
| | | | - Catherine Berry
- Institute of Molecular Cell and Systems Biology, University of Glasgow, Glasgow, UK
| | - Kaustabh Kumar Maiti
- Chemical Sciences and Technology Division, Organic Chemistry Section, Council of Scientific and Industrial Research–National Institute for Interdisciplinary Science and Technology, Thiruvananthapuram, India
| | - Sreelekha Therakathinal Thankappan
- Laboratory of Biopharmaceuticals and Nanomedicine, Division of Cancer Research, Regional Cancer Centre, Thiruvananthapuram, India (Research Centre, University of Kerala)
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23
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Mesenchymal Stem Cells for Treatment of Delayed-Healing Tympanic Membrane Perforations Using Hyaluronate-based Laminas as a Delivery System. Otol Neurotol 2022; 43:e497-e506. [DOI: 10.1097/mao.0000000000003468] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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24
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Schulman CI, Namias N, Pizano L, Rodriguez-Menocal L, Aickara D, Guzman W, Candanedo A, Maranda E, Beirn A, Badiavas EV. The effect of mesenchymal stem cells improves the healing of burn wounds: a phase 1 dose-escalation clinical trial. Scars Burn Heal 2022; 8:20595131211070783. [PMID: 35781931 PMCID: PMC9247372 DOI: 10.1177/20595131211070783] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022] Open
Abstract
Background Stem cell therapy holds promise to improve healing and stimulate tissue
regeneration after burn injury. Preclinical evidence has supported this;
however, clinical studies are lacking. We examined the application of bone
marrow-derived mesenchymal stem cells (BM-MSC) to deep second-degree burn
injuries using a two-dose escalation protocol. Methods Ten individuals aged 18 years or older with deep second-degree burn wounds
were enrolled. The first five patients were administered 2.5 × 10³
BM-MSC/cm2 to their wounds. After safety of the initial dose
level was assessed, a second group of five patients was treated with a
higher concentration of 5 × 10³ allogeneic BM-MSC/cm2. Safety was
assessed clinically and by evaluating cytokine levels in mixed recipient
lymphocyte/donor BM-MSC reactions (INFγ, IL-10 and TNFα). At each visit, we
performed wound measurements and assessed wounds using a Patient and
Observer Scar Assessment Scale (POSAS). Results All patients responded well to treatment, with 100% closure of wounds and
minimal clinical evidence of fibrosis. No adverse reactions or evidence of
rejection were observed for both dose levels. Patients receiving the first
dose concentration had a wound closure rate of 3.64 cm2/day.
Patients receiving the second dose concentration demonstrated a wound
closure rate of 10.47 cm2/day. The difference in healing rates
between the two groups was not found to be statistically significant
(P = 0.17). Conclusion BM-MSC appear beneficial in optimising wound healing in patients with deep
second-degree burn wounds. Adverse outcomes were not observed when
administering multiple doses of allogeneic BM-MSC. Lay Summary Thermal injuries are a significant source of morbidity and mortality,
constituting 5%–20% of all injuries and 4% of all deaths. Despite overall
improvements in the management of acutely burned patients, morbidities
associated with deeper burn injuries remain commonplace. Burn patients are
too often left with significant tissue loss, scarring and contractions
leading to physical loss of function and long-lasting psychological and
emotional impacts. In previous studies, we have demonstrated the safety and efficacy of
administering bone marrow-derived mesenchymal stem cells (BM-MSC) to chronic
wounds with substantial improvement in healing and evidence of tissue
regeneration. In this report, we have examined the application of BM-MSC to
deep second-degree burn injuries in patients. The aim of the present phase I/II clinical trial was to examine the safety
and efficacy of administering allogeneic BM-MSC to deep second-degree burns.
We utilised two different dose levels at concentrations 2.5 × 103
and 5 × 103 cells/cm2. Patients with deep
second-degree burn wounds up to 20% of the total body surface area were
eligible for treatment. Allogeneic BM-MSC were applied to burn wounds
topically or by injection under transparent film dressing <7 days after
injury. Patients were followed for at least six months after treatment. Using two dose levels allowed us to gain preliminary information as to
whether different amounts of BM-MSC administered to burn wounds will result
in significant differences in safety/ clinical response. Once the safety and
dose-response analysis were completed, we evaluated the efficacy of
allogeneic stem cell therapy in the treatment of deep second-degree burn
wounds. In this study, we examined the role of allogeneic BM-MSC treatment in
patients with deep second-degree burn injuries, in a dose-dependent manner.
No significant related adverse events were reported. Safety was evaluated
both clinically and by laboratory-based methods. Efficacy was assessed
clinically through evidence of re-pigmentation, hair follicle restoration
and regenerative change. While these findings are encouraging, more studies
will be needed to better establish the benefit of BM-MSC in the treatment of
burn injuries.
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Affiliation(s)
- Carl I Schulman
- Department of Surgery, Ryder Trauma Center, University of Miami School of Medicine, Miami, FL, USA
| | - Nicholas Namias
- Department of Surgery, Ryder Trauma Center, University of Miami School of Medicine, Miami, FL, USA
| | - Louis Pizano
- Department of Surgery, Ryder Trauma Center, University of Miami School of Medicine, Miami, FL, USA
| | - Luis Rodriguez-Menocal
- Department of Dermatology and Cutaneous Surgery. Leonard M Miller School of Medicine, University of Miami, Interdisciplinary Stem Cell Institute, Miami, FL, USA
| | - Divya Aickara
- Department of Dermatology and Cutaneous Surgery. Leonard M Miller School of Medicine, University of Miami, Interdisciplinary Stem Cell Institute, Miami, FL, USA
| | - Wellington Guzman
- Department of Surgery, Ryder Trauma Center, University of Miami School of Medicine, Miami, FL, USA
| | - Ambar Candanedo
- Department of Surgery, Ryder Trauma Center, University of Miami School of Medicine, Miami, FL, USA
| | - Eric Maranda
- Department of Dermatology and Cutaneous Surgery. Leonard M Miller School of Medicine, University of Miami, Interdisciplinary Stem Cell Institute, Miami, FL, USA
| | - Audrey Beirn
- Department of Dermatology and Cutaneous Surgery. Leonard M Miller School of Medicine, University of Miami, Interdisciplinary Stem Cell Institute, Miami, FL, USA
| | - Evangelos V Badiavas
- Department of Dermatology and Cutaneous Surgery. Leonard M Miller School of Medicine, University of Miami, Interdisciplinary Stem Cell Institute, Miami, FL, USA
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25
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Malhotra P, Shukla M, Meena P, Kakkar A, Khatri N, Nagar RK, Kumar M, Saraswat SK, Shrivastava S, Datt R, Pandey S. Mesenchymal stem cells are prospective novel off-the-shelf wound management tools. Drug Deliv Transl Res 2022; 12:79-104. [PMID: 33580481 DOI: 10.1007/s13346-021-00925-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/25/2021] [Indexed: 12/12/2022]
Abstract
Chronic/non-healing cutaneous wounds pose a debilitating burden on patients and healthcare system. Presently, treatment modalities are rapidly shifting pace from conventional methods to advanced wound care involving cell-based therapies. Mesenchymal stem cells (MSCs) have come across as a prospective option due to its pleiotropic functions viz. non-immunogenicity, multipotency, multi-lineage plasticity and secretion of growth factors, cytokines, microRNAs (miRNA), exosomes, and microvesicles as part of their secretome for assisting wound healing. We outline the therapeutic role played by MSCs and its secretome in suppressing tissue inflammation, causing immunomodulation, aiding angiogenesis and assisting in scar-free wound healing. We further assess the mechanism of action by which MSCs contribute in manifesting tissue repair. The review flows ahead in exploring factors that influence healing behavior including effect of multiple donor sites, donor age and health status, tissue microenvironment, and in vitro expansion capability. Moving ahead, we overview the advancements achieved in extending the lifespan of cells upon implantation, influence of genetic modifications aimed at altering MSC cargo, and evaluating bioengineered matrix-assisted delivery methods toward faster healing in preclinical and clinical models. We also contribute toward highlighting the challenges faced in commercializing cell-based therapies as standard of care treatment regimens. Finally, we strongly advocate and highlight its application as a futuristic technology for revolutionizing tissue regeneration.
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Affiliation(s)
- Poonam Malhotra
- Department of Life Sciences, Datt Mediproducts Private Ltd, Roz Ka Meo Industrial Area, Distt. Mewat, Nuh, 122103, Haryana, India
| | - Manish Shukla
- Department of Life Sciences, Datt Mediproducts Private Ltd, Roz Ka Meo Industrial Area, Distt. Mewat, Nuh, 122103, Haryana, India
| | - Poonam Meena
- Department of Life Sciences, Datt Mediproducts Private Ltd, Roz Ka Meo Industrial Area, Distt. Mewat, Nuh, 122103, Haryana, India
| | - Anupama Kakkar
- Department of Life Sciences, Datt Mediproducts Private Ltd, Roz Ka Meo Industrial Area, Distt. Mewat, Nuh, 122103, Haryana, India
| | - Nitin Khatri
- Department of Life Sciences, Datt Mediproducts Private Ltd, Roz Ka Meo Industrial Area, Distt. Mewat, Nuh, 122103, Haryana, India
| | - Rakesh K Nagar
- Department of Life Sciences, Datt Mediproducts Private Ltd, Roz Ka Meo Industrial Area, Distt. Mewat, Nuh, 122103, Haryana, India
| | - Mukesh Kumar
- Department of Life Sciences, Datt Mediproducts Private Ltd, Roz Ka Meo Industrial Area, Distt. Mewat, Nuh, 122103, Haryana, India
| | - Sumit K Saraswat
- Department of Life Sciences, Datt Mediproducts Private Ltd, Roz Ka Meo Industrial Area, Distt. Mewat, Nuh, 122103, Haryana, India
| | - Supriya Shrivastava
- Department of Life Sciences, Datt Mediproducts Private Ltd, Roz Ka Meo Industrial Area, Distt. Mewat, Nuh, 122103, Haryana, India
| | - Rajan Datt
- Department of Life Sciences, Datt Mediproducts Private Ltd, Roz Ka Meo Industrial Area, Distt. Mewat, Nuh, 122103, Haryana, India
| | - Siddharth Pandey
- Department of Life Sciences, Datt Mediproducts Private Ltd, Roz Ka Meo Industrial Area, Distt. Mewat, Nuh, 122103, Haryana, India.
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Riedl J, Popp C, Eide C, Ebens C, Tolar J. Mesenchymal stromal cells in wound healing applications: role of the secretome, targeted delivery and impact on recessive dystrophic epidermolysis bullosa treatment. Cytotherapy 2021; 23:961-973. [PMID: 34376336 PMCID: PMC8569889 DOI: 10.1016/j.jcyt.2021.06.004] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Revised: 05/25/2021] [Accepted: 06/22/2021] [Indexed: 12/12/2022]
Abstract
Mesenchymal stromal cells (MSCs) are multi-potent stromal-derived cells capable of self-renewal that possess several advantageous properties for wound healing, making them of interest to the field of dermatology. Research has focused on characterizing the unique properties of MSCs, which broadly revolve around their regenerative and more recently discovered immunomodulatory capacities. Because of ease of harvesting and expansion, differentiation potential and low immunogenicity, MSCs have been leading candidates for tissue engineering and regenerative medicine applications for wound healing, yet results from clinical studies have been variable, and promising pre-clinical work has been difficult to reproduce. Therefore, the specific mechanisms of how MSCs influence the local microenvironment in distinct wound etiologies warrant further research. Of specific interest in MSC-mediated healing is harnessing the secretome, which is composed of components known to positively influence wound healing. Molecules released by the MSC secretome can promote re-epithelialization and angiogenesis while inhibiting fibrosis and microbial invasion. This review focuses on the therapeutic interest in MSCs with regard to wound healing applications, including burns and diabetic ulcers, with specific attention to the genetic skin disease recessive dystrophic epidermolysis bullosa. This review also compares various delivery methods to support skin regeneration in the hopes of combating the poor engraftment of MSCs after delivery, which is one of the major pitfalls in clinical studies utilizing MSCs.
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Affiliation(s)
- Julia Riedl
- Medical Scientist Training Program (MD/PhD), University of Minnesota, Minneapolis, Minnesota, USA; Stem Cell Institute, University of Minnesota, Minneapolis, Minnesota, USA
| | - Courtney Popp
- Division of Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA
| | - Cindy Eide
- Division of Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA
| | - Christen Ebens
- Division of Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA
| | - Jakub Tolar
- Division of Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA; Stem Cell Institute, University of Minnesota, Minneapolis, Minnesota, USA.
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A Beginner's Introduction to Skin Stem Cells and Wound Healing. Int J Mol Sci 2021; 22:ijms222011030. [PMID: 34681688 PMCID: PMC8538579 DOI: 10.3390/ijms222011030] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Revised: 10/06/2021] [Accepted: 10/11/2021] [Indexed: 02/06/2023] Open
Abstract
The primary function of the skin is that of a physical barrier against the environment and diverse pathogens; therefore, its integrity is essential for survival. Skin regeneration depends on multiple stem cell compartments within the epidermis, which, despite their different transcriptional and proliferative capacity, as well as different anatomical location, fall under the general term of skin stem cells (SSCs). Skin wounds can normally heal without problem; however, some diseases or extensive damage may delay or prevent healing. Non-healing wounds represent a serious and life-threatening scenario that may require advanced therapeutic strategies. In this regard, increased focus has been directed at SSCs and their role in wound healing, although emerging therapeutical approaches are considering the use of other stem cells instead, such as mesenchymal stem cells (MSCs). Given its extensive and broad nature, this review supplies newcomers with an introduction to SSCs, wound healing, and therapeutic strategies for skin regeneration, thus familiarizing the reader with the subject in preparation for future in depth reading.
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Saha D, Thannimangalath S, Budamakuntla L, Loganathan E, Jamora C. Hair Follicle Grafting Therapy Promotes Re-Emergence of Critical Skin Components in Chronic Nonhealing Wounds. JID INNOVATIONS 2021; 1:100041. [PMID: 34909736 PMCID: PMC8659399 DOI: 10.1016/j.xjidi.2021.100041] [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: 03/30/2021] [Revised: 05/26/2021] [Accepted: 06/11/2021] [Indexed: 12/03/2022] Open
Abstract
An exploding public health crisis is the exponential growth in the incidence of chronic nonhealing ulcers associated with diseases such as diabetes. Various modalities have been developed to stimulate wound closure that is otherwise recalcitrant to standard clinical treatments. However, these approaches primarily focus on the process of re-epithelialization and are often deficient in regenerating the full spectrum of structures necessary for normal skin function. Autologous hair follicle grafting is a recent therapy to stimulate the closure of such nonhealing wounds, and we observed effects beyond the epidermis to other important components of the dermis. We found that hair follicle grafting facilitated the reappearance of various undifferentiated and differentiated layers of the epidermis with the restoration of epidermal junctions. In addition, other important structures that are critical for cutaneous health and function such as the blood and lymph vasculature, nerve fibers, and sweat gland structures were restored in postgrafted wounds. Interestingly, both immune cells and inflammatory signals were substantially decreased, indicating a reduction in the chronic inflammation that is a hallmark of nonhealing wounds. Our observation that punch wounds created on the postgrafted area likewise healed suggests that this is a self-sustaining long-term therapy for patients with chronic wounds.
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Affiliation(s)
- Dyuti Saha
- IFOM-inStem Joint Research Laboratory, Centre for Inflammation and Tissue Homeostasis, Institute for Stem Cell Science and Regenerative Medicine, Bangalore, India
- Department of Biology, Manipal Academy of Higher Education, Manipal, India
| | - Sujaya Thannimangalath
- IFOM-inStem Joint Research Laboratory, Centre for Inflammation and Tissue Homeostasis, Institute for Stem Cell Science and Regenerative Medicine, Bangalore, India
| | - Leelavathy Budamakuntla
- Department of Dermatology, Bangalore Medical College and Research Institute, Bangalore, India
| | - Eswari Loganathan
- Department of Dermatology, Bangalore Medical College and Research Institute, Bangalore, India
| | - Colin Jamora
- IFOM-inStem Joint Research Laboratory, Centre for Inflammation and Tissue Homeostasis, Institute for Stem Cell Science and Regenerative Medicine, Bangalore, India
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29
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Choudhury S, Surendran N, Das A. Recent advances in the induced pluripotent stem cell-based skin regeneration. Wound Repair Regen 2021; 29:697-710. [PMID: 33970525 DOI: 10.1111/wrr.12925] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2020] [Revised: 03/30/2021] [Accepted: 04/27/2021] [Indexed: 01/05/2023]
Abstract
Skin regeneration has been a challenging clinical problem especially in cases of chronic wounds such as diabetic foot ulcers, and epidermolysis bullosa-related skin blisters. Prolonged non-healing wounds often lead to bacterial infections increasing the severity of wounds. Current treatment strategies for chronic wounds include debridement of wounds along with antibiotics, growth factors, and stem cell transplantation therapies. However, the compromised nature of autologous stem cells in patients with comorbidities such as diabetes limits the efficacy of the therapy. The discovery of induced pluripotent stem cell (iPSC) technology has immensely influenced the field of regenerative therapy. Enormous efforts have been made to develop integration-free iPSCs suitable for clinical therapies. This review focuses on recent advances in the methods and reprogramming factors for generating iPSCs along with the existing challenges such as genetic alterations, tumorigenicity, immune rejection, and regulatory hurdles for the clinical application of iPSCs. Furthermore, this review also highlights the benefits of using iPSCs for the generation of skin cells and skin disease modeling over the existing clinical therapies for skin regeneration in chronic wounds and skin diseases.
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Affiliation(s)
- Subholakshmi Choudhury
- Department of Applied Biology, Council of Scientific & Industrial Research-Indian Institute of Chemical Technology (CSIR-IICT), Hyderabad, India
- Academy of Science and Innovative Research (AcSIR), Ghaziabad, India
| | - Nidhi Surendran
- Department of Applied Biology, Council of Scientific & Industrial Research-Indian Institute of Chemical Technology (CSIR-IICT), Hyderabad, India
| | - Amitava Das
- Department of Applied Biology, Council of Scientific & Industrial Research-Indian Institute of Chemical Technology (CSIR-IICT), Hyderabad, India
- Academy of Science and Innovative Research (AcSIR), Ghaziabad, India
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30
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Does intraurethral erythropoietin administration effect wound healing after hypospadias correction? an experimental rat study. Int Urol Nephrol 2021; 53:2057-2062. [PMID: 34132972 DOI: 10.1007/s11255-021-02912-9] [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: 04/08/2021] [Accepted: 06/03/2021] [Indexed: 10/21/2022]
Abstract
OBJECTIVES To analyze effects of intraurethral EPO application on urethral wound healing by defining hystopathologic changes in a rat model of hypospadias. METHODS A hypospadias model was created in 30 rats and randomized into 3 groups of 10. For 14 days, the first group was administered 25 iu EPO instillation intraurethrally once a day, while group 2 was administered with 50 iu EPO in the same manner. The third group was assigned as control group. On the day 15, rats were sacrificed and penectomies were performed. One independent pathologist who is blinded to groups and treatments evaluated the penis samples. RESULTS Histopathologic examinations yielded the mean fibrosis scores (± SD) as 1.9 ± 0.568, 1.1 ± 0.786 and 2.5 ± 0.535 in groups I, II and III, respectively. There was significant difference between the EPO groups and the control group (p = 0.04-I, p = 0.003-II). The mean inflammation scar scores (± SD) were determined as 1 ± 1.054, 2 ± 1.247, 2.63 ± 0.744 in groups I, II and III, respectively. There was a significant difference in terms of inflammation between control group and group I (p = 0.005). Mean congestion scores (± SD) were found 1.2 ± 0.789 in groups I-II and 0.75 ± 0.463 in group III (p = 0.310). Hyperemia was seen in 60% 70% and 37.5% in groups I, II and III, respectively (p = 0.387). CONCLUSION Intraurethral EPO therapy effected urethral wound healing in a good way. Thus it could be feasible to treat the patients with after hypospadias surgeries and to improve success rates.
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31
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Proteomic analysis of bone marrow-derived mesenchymal stem cell extracellular vesicles from healthy donors: implications for proliferation, angiogenesis, Wnt signaling, and the basement membrane. Stem Cell Res Ther 2021; 12:328. [PMID: 34090527 PMCID: PMC8180068 DOI: 10.1186/s13287-021-02405-7] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Accepted: 05/19/2021] [Indexed: 02/07/2023] Open
Abstract
Background Bone marrow-derived mesenchymal stem cells (BM-MSCs) have shown therapeutic potential in various in vitro and in vivo studies in cutaneous wound healing. Furthermore, there are ubiquitous studies highlighting the pro-regenerative effects of BM-MSC extracellular vesicles (BM-MSC EVs). The similarities and differences in BM-MSC EV cargo among potential healthy donors are not well understood. Variation in EV protein cargo is important to understand, as it may be useful in identifying potential therapeutic applications in clinical trials. We hypothesized that the donors would share both important similarities and differences in cargo relating to cell proliferation, angiogenesis, Wnt signaling, and basement membrane formation—processes shown to be critical for effective cutaneous wound healing. Methods We harvested BM-MSC EVs from four healthy human donors who underwent strict screening for whole bone marrow donation and further Good Manufacturing Practices-grade cell culture expansion for candidate usage in clinical trials. BM-MSC EV protein cargo was determined via mass spectrometry and Proteome Discoverer software. Corresponding proteomic networks were analyzed via the UniProt Consortium and STRING consortium databases. Results More than 3000 proteins were identified in each of the donors, sharing > 600 proteins among all donors. Despite inter-donor variation in protein identities, there were striking similarities in numbers of proteins per biological functional category. In terms of biologic function, the proteins were most associated with transport of ions and proteins, transcription, and the cell cycle, relating to cell proliferation. The donors shared essential cargo relating to angiogenesis, Wnt signaling, and basement membrane formation—essential processes in modulating cutaneous wound repair. Conclusions Healthy donors of BM-MSC EVs contain important similarities and differences among protein cargo that may play important roles in their pro-regenerative functions. Further studies are needed to correlate proteomic signatures to functional outcomes in cutaneous repair.
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32
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Chailakhyan RK, Mishina ES, Grosheva AG, Vorob'eva NN, Khachiyants VI, Inshakov YM, Gerasimov YV, Kuralesova AI, Moskvina IL. Comparative Morphological Study of the Formation of Reparative Regenerate during Skin Wound Healing in Rats under the Effect of Drugs and Bone Marrow. Bull Exp Biol Med 2021; 171:134-140. [PMID: 34050835 DOI: 10.1007/s10517-021-05185-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2020] [Indexed: 11/25/2022]
Abstract
We studied the formation of the reparative regenerate of the skin wound in rats under the effect of drug products based on keratan and secretome of bone marrow mesenchymal stem cells (MSC), as well as bone marrow cells (native and exposed to laser radiation with a wavelength of 1.56 μm). Due to the biological affinity for the dermal tissue, keratan preparations being applied to the skin stimulate regeneration of the wound defect. This substance in the form of a gel is characterized by high diffusion capacity, penetrates into the deeper layers of the dermis, and promotes the growth of the granulation tissue. Application of an ointment prepared on the basis of MSC secretome promotes quick transition of the healing process from the inflammatory to the regenerative stage. Thus, bone marrow cells were successfully used for skin wound healing. The results of the use of bone marrow cells for the healing of skin wounds were successful; bone marrow exposed to laser radiation demonstrated high efficiency in promoting reparative processes.
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Affiliation(s)
- R K Chailakhyan
- N. F. Gamaleya National Research Center of Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Moscow, Russia.
| | - E S Mishina
- Kursk State Medical University, Kursk, Russia
| | - A G Grosheva
- N. F. Gamaleya National Research Center of Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Moscow, Russia
| | - N N Vorob'eva
- Institute of Photonic Technologies, Federal Research Center "Crystallography and Photonics", Russian Academy of Sciences, Moscow, Russia
| | | | - Yu M Inshakov
- N. F. Gamaleya National Research Center of Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Moscow, Russia
| | - Yu V Gerasimov
- N. F. Gamaleya National Research Center of Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Moscow, Russia
| | - A I Kuralesova
- N. F. Gamaleya National Research Center of Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Moscow, Russia
| | - I L Moskvina
- N. F. Gamaleya National Research Center of Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Moscow, Russia
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33
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Alavi-Farzaneh B, Shojaeian A, Banitalebi-Dehkordi M, Mirahmadi F, Mehri-Ghahfarrokhi A, Ghorbanpour A, Rahmati-Dehkordi S, Yazdani F. Effects of Xenogen Mesenchymal Stem Cells and Cryo-Platelet Gel on Intractable Wound Healing in Animal. Antiinflamm Antiallergy Agents Med Chem 2021; 20:344-352. [PMID: 33992068 DOI: 10.2174/1871523020666210514002722] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2020] [Revised: 12/27/2020] [Accepted: 02/04/2021] [Indexed: 11/22/2022]
Abstract
BACKGROUND Today, the effects of growth factors and mesenchymal stem cells (MSCs) in promoting wound healing have been confirmed. OBJECTIVE This study aimed to investigate the effect of MSCs and platelet cryogel on wound healing. METHODS 40 male Wistar rats were randomly divided into five groups (n=8). The control group just dressed, the second group received platelet cryogel, the third group received platelet cryogel containing MSCs, the fourth group received plasma, and the fifth group received plasma plus MSCs. The biopsy was obtained from the wounds in 2, 4, 6, and 8 days of the treatment. Then pathological evaluation was conducted. Finally, qRT-PCR was performed to determine angiogenesis. RESULTS The intervention groups had faster wound healing and lower wound area than the control group (p<0.05). The highest wound healing rate and the smallest wound area were observed in the group after receiving platelet cryogel plus MSCs. Angiogenesis, fibrosis, myoepithelial and epithelialization in the pathologic examination using H & E staining were not significantly different between the groups. The expression of Ang-1 in the intervention groups was higher than the control group and the highest expression was observed in the platelet cryogel plus MSCs, followed by the platelet cryogel group. The expression of VEGF in the plasma plus MSCs was higher than in the other groups. CONCLUSION Further studies require to determine the effects of combined use of platelet cryogel plus MSCs on other types of wounds and evaluate mechanisms involved in wound healing like collagenases and inflammatory factors.
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Affiliation(s)
- Babak Alavi-Farzaneh
- Department of Surgery, School of Medicine, Kashani Hospital Shahrekord University of Medical Sciences, Iran
| | - Ali Shojaeian
- Department of Molecular Medicine, School of Advanced Technologies, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Mehdi Banitalebi-Dehkordi
- Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Fatemeh Mirahmadi
- Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Ameneh Mehri-Ghahfarrokhi
- Department of Molecular Medicine, School of Advanced Technologies, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Alireza Ghorbanpour
- Department of Surgery, School of Medicine, Kashani Hospital Shahrekord University of Medical Sciences, Iran
| | - Shima Rahmati-Dehkordi
- Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Farshad Yazdani
- Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
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34
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Cao Y, Yan J, Liu H. [Clinical research progress of mesenchymal stem cells in treatment of chronic wounds]. ZHONGGUO XIU FU CHONG JIAN WAI KE ZA ZHI = ZHONGGUO XIUFU CHONGJIAN WAIKE ZAZHI = CHINESE JOURNAL OF REPARATIVE AND RECONSTRUCTIVE SURGERY 2021; 35:496-501. [PMID: 33855836 DOI: 10.7507/1002-1892.202011009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
Objective To review the clinical research progress of mesenchymal stem cells (MSCs) in the treatment of chronic wounds. Methods The literature related to the chronic wound repair with MSCs at home and abroad in recent years was extensively reviewed, and the possible mechanism of MSCs in the treatment of chronic wounds, as well as its application and existing problems were summarized. Results MSCs can participate in all aspects of chronic wound healing to promote wound healing, and has shown broad application prospects in clinical trials. MSCs commonly used in clinical research include bone marrow-derived MSCs, adipose-derived tissue MSCs, and umbilical cord-derived MSCs. Conclusion MSCs treatment is a promising strategy for the chronic wounds, but there are still many problems in its widespread clinical application that require further research.
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Affiliation(s)
- Yingxuan Cao
- Department of Plastic Surgery, the First Affiliated Hospital of Jinan University, Innovative Technology Research Institute of Tissue Repair and Regeneration, Key Laboratory of Regenerative Medicine, Ministry of Education, Guangzhou Guangdong, 510630, P.R.China
| | - Jianxin Yan
- Department of Plastic Surgery, the First Affiliated Hospital of Jinan University, Innovative Technology Research Institute of Tissue Repair and Regeneration, Key Laboratory of Regenerative Medicine, Ministry of Education, Guangzhou Guangdong, 510630, P.R.China
| | - Hongwei Liu
- Department of Plastic Surgery, the First Affiliated Hospital of Jinan University, Innovative Technology Research Institute of Tissue Repair and Regeneration, Key Laboratory of Regenerative Medicine, Ministry of Education, Guangzhou Guangdong, 510630, P.R.China
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35
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Ayavoo T, Murugesan K, Gnanasekaran A. Roles and mechanisms of stem cell in wound healing. Stem Cell Investig 2021; 8:4. [PMID: 33829056 DOI: 10.21037/sci-2020-027] [Citation(s) in RCA: 40] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2020] [Accepted: 01/27/2021] [Indexed: 01/02/2023]
Abstract
Wound healing phases comprise of highly synchronized process that begins due to a damage and restores the integrity of the injured tissues. Wound healing reduces the damage in tissue and supply sufficient oxygen and tissue perfusion, provide proper nourishment and humid wound healing atmosphere to re-establish the essential status of exaggerated parts. The untreated wound becomes susceptible for pus development, bacterial infection and complications like sepsis. Traditional and modern approaches are in practice to treat acute, open and chronic injuries, however, present wound care management has met with challenges and minimal positive effects. Stem cells have possible wound healing capability to overwhelm restrictions of the current wound care practices as it produces faster tissue regeneration in wound repair. Stem cells are unspecialized cells derived from adult body tissues and embryos that differentiate into any cell of an organism and capable of self-regeneration. The understanding on molecular mechanisms of stem cells has become the central and promising field in scientific study. This review focuses on the pre-existing traditional and modern treatments for wound healing, and types and roles of stem cells in wound care management. This review also focuses on the fundamental molecular characterization and factors influencing the molecular mechanisms of stem cells in wound healing.
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Affiliation(s)
- Thurga Ayavoo
- Centre of Research for Infectious Diseases and Phytochemical Studies, Quest International University Perak, Perak, Malaysia
| | - Karthikeyan Murugesan
- Centre of Research for Infectious Diseases and Phytochemical Studies, Quest International University Perak, Perak, Malaysia.,Department of Microbiology, Faculty of Medicine, Quest International University Perak, Perak, Malaysia
| | - Ashok Gnanasekaran
- Centre of Research for Infectious Diseases and Phytochemical Studies, Quest International University Perak, Perak, Malaysia.,Department of Microbiology, Faculty of Medicine, Quest International University Perak, Perak, Malaysia
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Sharma P, Kumar A, Dey AD, Behl T, Chadha S. Stem cells and growth factors-based delivery approaches for chronic wound repair and regeneration: A promise to heal from within. Life Sci 2021; 268:118932. [PMID: 33400933 DOI: 10.1016/j.lfs.2020.118932] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2020] [Revised: 12/03/2020] [Accepted: 12/12/2020] [Indexed: 02/06/2023]
Abstract
The sophisticated chain of cellular and molecular episodes during wound healing includes cell migration, cell proliferation, deposition of extracellular matrix, and remodelling and are onerous to replicate. Encapsulation of growth factors (GFs) and Stem cell-based (SCs) has been proclaimed to accelerate healing by transforming every phase associated with wound healing to enhance skin regeneration. Therapeutic application of mesenchymal stem cells (MSCs), embryonic stem cells (ESCs) and induced pluripotent stem cells (PSCs) provides aid in wound fixing, tissue integrity restoration and function of impaired tissue. Several scientific studies have established the essential role GFs in wound healing and their reduced degree in the chronic wound. The overall limitation includes half-life, unfriendly microhabitat abundant with protease, and inadequate delivery approaches results in decreased delivery of effective amounts in a suitable time-based fashion. Advancements in the area of reformative medicine as well as tissue engineering have offered techniques competent of dispensing SCs and GFs in site-oriented manner. The progress in nanotechnology-based approaches attracts researcher to study and evaluate the potential of this SCs and GFs based therapy in chronic wounds. These techniques embrace the polymeric regime viz., nano-formulations, hydrogels, liposomes, scaffolds, nanofibers, metallic nanoparticles, lipid-based nanoparticles and dendrimers that have established better retort through targeting tissues when GFs and SCs are transported via these humans made devices. Assumed the current problems, improvements in delivery approaches and difficulties offered by chronic wounds, we hope to show that encapsulation of SCs and GFs loaded nanoformulations therapies is the rational next step in improving wound care.
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Affiliation(s)
- Preety Sharma
- Chitkara College of Pharmacy, Chitkara University, Punjab, India
| | - Arun Kumar
- Chitkara College of Pharmacy, Chitkara University, Punjab, India.
| | - Asmita Deka Dey
- Chitkara College of Pharmacy, Chitkara University, Punjab, India
| | - Tapan Behl
- Chitkara College of Pharmacy, Chitkara University, Punjab, India
| | - Swati Chadha
- Chitkara College of Pharmacy, Chitkara University, Punjab, India
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Blanton CM, Clougherty CO. The Role of Bone Marrow Aspirate in Osseous and Soft Tissue Pathology. Clin Podiatr Med Surg 2021; 38:1-16. [PMID: 33220739 DOI: 10.1016/j.cpm.2020.08.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Bone marrow aspirate (BMA) is an emerging therapy that is gaining popularity for orthoplastic reconstruction. The stem cells collected are multipotent and regenerative in nature. In addition to stem cells, other biological components collected augment the mitogen of local cells, proliferation, and angiogenesis, and inhibit proinflammatory cytokine and bacteria to optimize an environment to heal. The most common site for harvest is the iliac crest. Techniques for harvesting BMA are simple to perform, financially modest, and associated with low morbidity. Additional research is needed to evolve and standardize the technology; however, BMA is proven to be advantageous for tissue repair.
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Affiliation(s)
- Casie M Blanton
- The Reconstruction Institute of The Bellevue Hospital, 102 Commerce Park Drive, Suite D, Bellevue, OH 44811, USA.
| | - Coleman O Clougherty
- The Reconstruction Institute of The Bellevue Hospital, 102 Commerce Park Drive, Suite D, Bellevue, OH 44811, USA
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Abstract
In the past decade, the frequency of chronic wounds in older population has increased, and their impact on quality of life is substantial. Chronic wounds are a public health problem associated with very high economic and psychosocial costs. These wounds result from various pathologies and comorbidities, such arterial and venous insufficiency, diabetes mellitus and continuous skin pressure. Recently, the role of infection and biofilms in the healing of chronic wounds has been the subject of considerable research. This paper presents an overview of various methods and products used to manage chronic wounds and discusses recent advances in wound care. To decide on the best treatment for any wound, it is crucial to holistically assess the patient and the wound. Additionally, multiple strategies could be used to prevent or treat chronic wounds.
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Affiliation(s)
- Maria Azevedo
- Researcher, Center for Research in Health Technologies and Information Systems and Department of Microbiology, Faculty of Medicine, University of Porto, Portugal
| | - Carmen Lisboa
- Lecturer and Researcher in Medical Microbiology, Center for Research in Health Technologies and Information Systems and Department of Microbiology, Faculty of Medicine, University of Porto, Portugal
| | - Acácio Rodrigues
- Lecturer and Researcher in Medical Microbiology, Faculty of Medicine, Porto; Burn Unit, Department of Plastic and Reconstructive Surgery, Hospital São João, Portugal
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Kumar A, Behl T, Chadha S. A rationalized and innovative perspective of nanotechnology and nanobiotechnology in chronic wound management. J Drug Deliv Sci Technol 2020. [DOI: 10.1016/j.jddst.2020.101930] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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Abstract
INTRODUCTION Transplantation of the keratinocytes, fibroblasts, bone marrow, and adipose tissue-derived mesenchymal stem cells may improve chronic wound healing by delivery of different cytokines, chemokines, and growth factors, which play an essential role in wound healing. The purposes of this review were to check which cell lines are potentially beneficial in enhancement of wound healing and to describe the safety and efficacy of cell therapies in the clinical treatment of chronic wounds, as well as to summarize the pertinent literature and research progress in this field. METHODS PubMed search engine and ClinicalTrials.gov were used to analyze the available data on cell therapies applied in treatment of chronic wound. The analysis included 51 articles, assessing the use of keratinocytes (10), fibroblasts (7), keratinocytes and fibroblasts (10), bone marrow-derived cells (20), and adipose tissue cells (4). Studies on the cell-based products that are currently available on the market (Dermagraft, EpiDex, Apligraf, and HP802-247) were also included, with majority of reports found on fibroblasts and keratinocytes studies. RESULTS Cell-based therapies have a great potential to improve wound healing without major surgical procedures and donor-site morbidity. There is, however, a lack of guidelines on how the age of the patients, the general health conditions, and the coexistence of different diseases may affect the success of these therapies. Further studies are needed to determine the fate of transplanted cells and the number of cells required to obtain optimal effects and outcomes. CONCLUSIONS Despite many promising clinical trials on application of various stem cell-based therapies for treatment of chronic wounds, there is still a need for multicenter comparative studies assessing the dose response and the cell source response on the efficacy of chronic wound healing.
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Nikam VS, Punde DS, Bhandari RS. Silk fibroin nanofibers enhance cell adhesion of blood-derived fibroblast-like cells: A potential application for wound healing. Indian J Pharmacol 2020; 52:306-312. [PMID: 33078732 PMCID: PMC7722904 DOI: 10.4103/ijp.ijp_609_19] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
AIM: The aim of this study is to evaluate silk-fibroin electrospun nanofibers and blood-derived fibroblast-like cells for cytotoxicity and cell adhesion. BACKGROUND: Silk fibroin (SF) has emerged as a favorable and potential bio-material owing to its unique properties such as biocompatibility, biodegradability, the possibility of functional modifications, mechanical strength, and regenerative capability. Despite current advancements in tissue engineering technologies, delay wound healing and scar formation remain unresolved. Bioequivalent skin graft having human fibroblast and keratinocytes (Apligraft®) has proven to be beneficial, but the cost is a limiting factor. OBJECTIVE: The blood born fibroblast-like cells express several growth factors, extracellular matrix proteins, and these factors are crucial in the various steps of the wound-healing process. SF is an idea polymer by the virtue of its multifaceted characteristics such as mechanical strength, biodegradability, improved cell attachment, biocompatibility, good elasticity, having application in biomedical, tissue engineering, and medicine. The objective of the present study is to evaluate SF as a biomaterial for making nanofibers scaffold and culturing blood-derived fibroblast-like cells on it for the potential application to wound site. MATERIALS AND METHODS: Blood-derived fibroblast-like cells evaluated for cytotoxicity, collagen 1 expression, and cell adhesion on SF electrospun nanofibers. The silk nanofibers were fabricated by the electrospinning method using silk-derived fibroin solution and analyzed for protein composition, viscosity, and further characterized using the Fourier transformed infrared spectroscopy. RESULTS: The SF nanofibers were nontoxic to the blood-derived fibroblast-like cells. It improved cell adhesion with collagen 1 expression. CONCLUSION: The composite scaffold of SF nanofibers with blood-derived fibroblast-like cells would be a potential healing patch for many types of wounds.
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Affiliation(s)
- Vandana S Nikam
- STESs, Smt. K. N. College of Pharmacy, S. P. Pune University, Pune, Maharashtra, India
| | - Dhanshree S Punde
- STESs, Smt. K. N. College of Pharmacy, S. P. Pune University, Pune, Maharashtra, India
| | - Raviraj S Bhandari
- STESs, Smt. K. N. College of Pharmacy, S. P. Pune University, Pune, Maharashtra, India
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A. Everts P, Flanagan II G, Rothenberg J, Mautner K. The Rationale of Autologously Prepared Bone Marrow Aspirate Concentrate for use in Regenerative Medicine Applications. Regen Med 2020. [DOI: 10.5772/intechopen.91310] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
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Raghuram AC, Yu RP, Lo AY, Sung CJ, Bircan M, Thompson HJ, Wong AK. Role of stem cell therapies in treating chronic wounds: A systematic review. World J Stem Cells 2020; 12:659-675. [PMID: 32843920 PMCID: PMC7415243 DOI: 10.4252/wjsc.v12.i7.659] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2020] [Revised: 05/03/2020] [Accepted: 05/27/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The impairment of cutaneous wound healing results in chronic, non-healing wounds that are caused by altered wound environment oxygenation, tissue injury, and permissive microbial growth. Current modalities for the treatment of these wounds inadequately address the complex changes involved in chronic wound pathogenesis. Consequently, stem cell therapies have emerged as a potential therapeutic modality to promote cutaneous regeneration through trophic and paracrine activity.
AIM To investigate current literature regarding use of stem cell therapies for the clinical treatment of chronic, non-healing wounds.
METHODS PubMed, EMBASE, Cochrane Library, Web of Science, and Scopus were queried with combinations of the search terms “mesenchymal stem cells,” “adult stem cells,” “embryonic stem cells,” “erythroid precursor cells,” “stem cell therapies,” and “chronic wounds” in order to find relevant articles published between the years of 2000 and 2019 to review a 20-year experience. Reference lists from the articles were reviewed to identify additional pertinent articles. Retrieved manuscripts (reviews, case reports/series, retrospective/prospective studies, and clinical trials) were evaluated by the authors for their depiction of clinical stem cell therapy use. Data were extracted from the articles using a standardized collection tool.
RESULTS A total of 43 articles describing the use of stem cell therapies for the treatment of chronic wounds were included in this review. While stem cell therapies have been explored in in vitro and in vivo applications in the past, recent efforts are geared towards assessing their clinical role. A review of the literature revealed that adipose-derived stem cells, bone marrow-derived stem cells, bone marrow-derived mononuclear cells, epidermally-derived mesenchymal stem cells, fibroblast stem cells, keratinocyte stem cells, placental mesenchymal stem cells, and umbilical cord mesenchymal stem cells have all been employed in the treatment of chronic wounds of various etiologies. Most recently, embryonic stem cells have emerged as a novel stem cell therapy with the capacity for multifaceted germ cell layer differentiation. With the capacity for self-renewal and differentiation, stem cells can enrich existing cell populations in chronic wounds in order to overcome barriers impeding the progression of wound healing. Further, stem cell therapies can be utilized to augment cell engraftment, signaling and activity, and resultant patient outcomes.
CONCLUSION Assessing observed clinical outcomes, potential for stem cell use, and relevant therapeutic challenges allows wound care stakeholders to make informed decisions regarding optimal treatment approaches for their patients’ chronic wounds.
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Affiliation(s)
- Anjali C Raghuram
- Division of Plastic and Reconstructive Surgery, Keck School of Medicine of USC, Los Angeles, CA 90033, United States
| | - Roy P Yu
- Division of Plastic and Reconstructive Surgery, Keck School of Medicine of USC, Los Angeles, CA 90033, United States
| | - Andrea Y Lo
- Division of Plastic and Reconstructive Surgery, Keck School of Medicine of USC, Los Angeles, CA 90033, United States
| | - Cynthia J Sung
- Division of Plastic and Reconstructive Surgery, Keck School of Medicine of USC, Los Angeles, CA 90033, United States
| | - Melissa Bircan
- Division of Plastic and Reconstructive Surgery, Keck School of Medicine of USC, Los Angeles, CA 90033, United States
| | - Holly J Thompson
- Wilson Dental Library, Herman Ostrow School of Dentistry of USC, Los Angeles, CA 90089, United States
| | - Alex K Wong
- Division of Plastic and Reconstructive Surgery, Keck School of Medicine of USC, Los Angeles, CA 90033, United States
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Das M, Mayilsamy K, Mohapatra SS, Mohapatra S. Mesenchymal stem cell therapy for the treatment of traumatic brain injury: progress and prospects. Rev Neurosci 2020; 30:839-855. [PMID: 31203262 DOI: 10.1515/revneuro-2019-0002] [Citation(s) in RCA: 82] [Impact Index Per Article: 16.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2019] [Accepted: 04/05/2019] [Indexed: 12/12/2022]
Abstract
Traumatic brain injury (TBI) is a major cause of injury-related mortality and morbidity in the USA and around the world. The survivors may suffer from cognitive and memory deficits, vision and hearing loss, movement disorders, and different psychological problems. The primary insult causes neuronal damage and activates astrocytes and microglia which evokes immune responses causing further damage to the brain. Clinical trials of drugs to recover the neuronal loss are not very successful. Regenerative approaches for TBI using mesenchymal stem cells (MSCs) seem promising. Results of preclinical research have shown that transplantation of MSCs reduced secondary neurodegeneration and neuroinflammation, promoted neurogenesis and angiogenesis, and improved functional outcome in the experimental animals. The functional improvement is not necessarily related to cell engraftment; rather, immunomodulation by molecular factors secreted by MSCs is responsible for the beneficial effects of this therapy. However, MSC therapy has a few drawbacks including tumor formation, which can be avoided by the use of MSC-derived exosomes. This review has focused on the research works published in the field of regenerative therapy using MSCs after TBI and its future direction.
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Affiliation(s)
- Mahasweta Das
- James A. Haley Veterans Hospital, Tampa, FL 33612, USA.,Department of Molecular Medicine, University of South Florida College of Medicine, Tampa, FL 33612, USA
| | - Karthick Mayilsamy
- James A. Haley Veterans Hospital, Tampa, FL 33612, USA.,Department of Molecular Medicine, University of South Florida College of Medicine, Tampa, FL 33612, USA
| | - Shyam S Mohapatra
- James A. Haley Veterans Hospital, Tampa, FL 33612, USA.,Department of Internal Medicine, University of South Florida College of Medicine, Tampa, FL 33612, USA
| | - Subhra Mohapatra
- James A. Haley Veterans Hospital, Tampa, FL 33612, USA.,Department of Molecular Medicine, University of South Florida College of Medicine, Tampa, FL 33612, USA
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Huang YZ, Gou M, Da LC, Zhang WQ, Xie HQ. Mesenchymal Stem Cells for Chronic Wound Healing: Current Status of Preclinical and Clinical Studies. TISSUE ENGINEERING PART B-REVIEWS 2020; 26:555-570. [PMID: 32242479 DOI: 10.1089/ten.teb.2019.0351] [Citation(s) in RCA: 118] [Impact Index Per Article: 23.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Healing skin wounds with anatomic and functional integrity, especially under chronic pathological conditions, remain an enormous challenge. Due to their outstanding regenerative potential, mesenchymal stem cells (MSCs) have been explored in many studies to determine the healing ability for difficult-to-treat diseases. In this article, we review current animal studies and clinical trials of MSC-based therapy for chronic wounds, and discuss major challenges that confront future clinical applications. We found that a wealth of animal studies have revealed the versatile roles and the benefits of MSCs for chronic wound healing. MSC treatment results in enhanced angiogenesis, facilitated reepithelialization, improved granulation, and accelerated wound closure. There are some evidences of the transdifferentiation of MSCs into skin cells. However, the healing effect of MSCs depends primarily on their paracrine actions, which alleviate the harsh microenvironment of chronic wounds and regulate local cellular responses. Consistent with the findings of preclinical studies, some clinical trials have shown improved wound healing after transplantation of MSCs in chronic wounds, mainly lower extremity ulcers, pressure sores, and radiation burns. However, there are some limitations in these clinical trials, especially a small number of patients and imperfect methodology. Therefore, to better define the safety and efficiency of MSC-based wound therapy, large-scale controlled multicenter trials are needed in the future. In addition, to build a robust pool of clinical evidence, standardized protocols, especially the cultivation and quality control of MSCs, are recommended. Altogether, based on current data, MSC-based therapy represents a promising treatment option for chronic wounds. Impact statement Chronic wounds persist as a significant health care problem, particularly with increasing number of patients and the lack of efficient treatments. The main goal of this article is to provide an overview of current status of mesenchymal stem cell (MSC)-based therapy for chronic wounds. The roles of MSCs in skin wound healing, as revealed in a large number of animal studies, are detailed. A critical view is made on the clinical application of MSCs for lower extremity ulcers, pressure sores, and radiation burns. Main challenges that confront future clinical applications are discussed, which hopefully contribute to innovations in MSC-based wound treatment.
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Affiliation(s)
- Yi-Zhou Huang
- Laboratory of Stem Cell and Tissue Engineering, Orthopaedic Research Institute, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China.,Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, China
| | - Min Gou
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Lin-Cui Da
- Fujian Provincial Maternity and Children's Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Wen-Qian Zhang
- Laboratory of Stem Cell and Tissue Engineering, Orthopaedic Research Institute, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
| | - Hui-Qi Xie
- Laboratory of Stem Cell and Tissue Engineering, Orthopaedic Research Institute, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China.,Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, China
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Multi-Spheroid-Loaded Human Acellular Dermal Matrix Carrier Preserves Its Spheroid Shape and Improves In Vivo Adipose-Derived Stem Cell Delivery and Engraftment. Tissue Eng Regen Med 2020; 17:271-283. [PMID: 32314311 DOI: 10.1007/s13770-020-00252-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2020] [Revised: 03/09/2020] [Accepted: 03/15/2020] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Current in vivo adult stem cell delivery presents limited clinical effects due to poor engraftment and survival. To overcome current challenges in cell delivery and promote surgical cell delivery for soft tissue repair, a multi-spheroid-loaded thin sectioned acellular dermal matrix (tsADM) carrier which preserves loaded spheroids' three-dimensional (3D) structure, was developed. METHODS Adipose-derived stem cells (ASCs) were used for spheroid delivery. After generating spheroids in 3D cell culture dishes, spheroid plasticity and survival in-between coverslips were evaluated. Spheroids were loaded onto tsADM, their shape changes were followed up for 14 days, and then imaged. Spheroid adhesion stability to tsADM against shear stress was also evaluated. Finally, cell delivery efficacy was compared with cell-seeded tsADM by in vivo implantation and histological evaluation. RESULTS Spheroids withstood cyclic compression stress and maintained their 3D shape without fusion after 48 h of culture in-between coverslips. Cell survival improved when spheroids were cultured on tsADM in-between the coverslips. Spheroid-loaded tsADM with coverslips maintained their spheroid outline for 14 days of culture whereas without coverslips, the group lost their outline due to spreading after 4 days in culture. Spheroids loaded onto tsADMs were more stable after six rather than 3 days in culture. Spheroid-loaded tsADMs showed about a 2.96-fold higher ASCs transplantation efficacy than cell-seeded tsADMs after 2 weeks of in vivo transplantation. CONCLUSION These results indicate that transplantation of spheroid-loaded tsADMs significantly improved cell delivery. These findings suggest that a combined approach with other cells, drugs, and nanoparticles may improve cell delivery and therapeutic efficacy.
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Munir S, Basu A, Maity P, Krug L, Haas P, Jiang D, Strauss G, Wlaschek M, Geiger H, Singh K, Scharffetter-Kochanek K. TLR4-dependent shaping of the wound site by MSCs accelerates wound healing. EMBO Rep 2020; 21:e48777. [PMID: 32162777 PMCID: PMC7202058 DOI: 10.15252/embr.201948777] [Citation(s) in RCA: 42] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2019] [Revised: 02/14/2020] [Accepted: 02/18/2020] [Indexed: 12/13/2022] Open
Abstract
We here address the question whether the unique capacity of mesenchymal stem cells to re‐establish tissue homeostasis depends on their potential to sense pathogen‐associated molecular pattern and, in consequence, mount an adaptive response in the interest of tissue repair. After injection of MSCs primed with the bacterial wall component LPS into murine wounds, an unexpected acceleration of healing occurs, clearly exceeding that of non‐primed MSCs. This correlates with a fundamental reprogramming of the transcriptome in LPS‐treated MSCs as deduced from RNAseq analysis and its validation. A network of genes mediating the adaptive response through the Toll‐like receptor 4 (TLR4) pathway responsible for neutrophil and macrophage recruitment and their activation profoundly contributes to enhanced wound healing. In fact, injection of LPS‐primed MSCs silenced for TLR4 fails to accelerate wound healing. These unprecedented findings hold substantial promise to refine current MSC‐based therapies for difficult‐to‐treat wounds.
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Affiliation(s)
- Saira Munir
- Department of Dermatology and Allergic Diseases, Ulm University, Ulm, Germany
| | - Abhijit Basu
- Department of Dermatology and Allergic Diseases, Ulm University, Ulm, Germany
| | - Pallab Maity
- Department of Dermatology and Allergic Diseases, Ulm University, Ulm, Germany.,Aging Research Center (ARC), Ulm, Germany
| | - Linda Krug
- Department of Dermatology and Allergic Diseases, Ulm University, Ulm, Germany.,Aging Research Center (ARC), Ulm, Germany
| | - Philipp Haas
- Department of Dermatology and Allergic Diseases, Ulm University, Ulm, Germany
| | - Dongsheng Jiang
- Comprehensive Pneumology Center, Institute of Lung Biology and Disease, Helmholtz Zentrum München, Munich, Germany
| | - Gudrun Strauss
- Department of Pediatrics and Adolescent Medicine, Ulm University, Ulm, Germany
| | - Meinhard Wlaschek
- Department of Dermatology and Allergic Diseases, Ulm University, Ulm, Germany
| | - Hartmut Geiger
- Department of Dermatology and Allergic Diseases, Ulm University, Ulm, Germany.,Aging Research Center (ARC), Ulm, Germany.,Institute of Molecular Medicine and Stem Cell Aging, Ulm University, Ulm, Germany.,Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | - Karmveer Singh
- Department of Dermatology and Allergic Diseases, Ulm University, Ulm, Germany.,Aging Research Center (ARC), Ulm, Germany
| | - Karin Scharffetter-Kochanek
- Department of Dermatology and Allergic Diseases, Ulm University, Ulm, Germany.,Aging Research Center (ARC), Ulm, Germany
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Tissue Engineering and Regenerative Medicine in Craniofacial Reconstruction and Facial Aesthetics. J Craniofac Surg 2020; 31:15-27. [PMID: 31369496 DOI: 10.1097/scs.0000000000005840] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
The craniofacial region is anatomically complex and is of critical functional and cosmetic importance, making reconstruction challenging. The limitations of current surgical options highlight the importance of developing new strategies to restore the form, function, and esthetics of missing or damaged soft tissue and skeletal tissue in the face and cranium. Regenerative medicine (RM) is an expanding field which combines the principles of tissue engineering (TE) and self-healing in the regeneration of cells, tissues, and organs, to restore their impaired function. RM offers many advantages over current treatments as tissue can be engineered for specific defects, using an unlimited supply of bioengineered resources, and does not require immunosuppression. In the craniofacial region, TE and RM are being increasingly used in preclinical and clinical studies to reconstruct bone, cartilage, soft tissue, nerves, and blood vessels. This review outlines the current progress that has been made toward the engineering of these tissues for craniofacial reconstruction and facial esthetics.
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López-Beas J, Guadix JA, Clares B, Soriano-Ruiz JL, Zugaza JL, Gálvez-Martín P. An overview of international regulatory frameworks for mesenchymal stromal cell-based medicinal products: From laboratory to patient. Med Res Rev 2020; 40:1315-1334. [PMID: 32017179 DOI: 10.1002/med.21659] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2019] [Revised: 01/14/2020] [Accepted: 01/22/2020] [Indexed: 12/12/2022]
Abstract
Human mesenchymal stromal cells (hMSCs) are emerging as one of the most important cell types in advanced therapies and regenerative medicine due to their great therapeutic potential. The development of hMSC-based products focuses on the use of hMSCs as biological active substances, and they are considered medicinal products by the primary health agencies worldwide. Due to their regulatory status, the development of hMSC-based products is regulated by specific criteria that range from the design phase, nonclinical studies, clinical studies, to the final registration and approval. Patients should only be administered hMSC-based products within the framework of a clinical trial or after the product has obtained marketing authorization; in both cases, authorization by health authorities is usually required. Considering the above, this paper describes the current general regulatory requirements for hMSC-based products, by jurisdiction, to be implemented throughout their entire development process. These measures may provide support for researchers from both public and private entities and academia to optimize the development of these products and their subsequent marketing, thereby improving access to them by patients.
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Affiliation(s)
- Javier López-Beas
- Andalusian Center for Molecular Biology and Regenerative Medicine (CABIMER), University of Pablo de Olavide-University of Seville-CSIC, Seville, Spain
| | - Juan A Guadix
- Department of Animal Biology, Faculty of Sciences, Instituto Malagueño de Biomedicina (IBIMA), Campus de Teatinos s/n, University of Málaga, Málaga, Spain.,BIONAND, Centro Andaluz de Nanomedicina y Biotecnología (Junta de Andalucía, Universidad de Málaga), Málaga, Spain
| | - Beatriz Clares
- Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Granada, Granada, Spain
| | - Jose L Soriano-Ruiz
- Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Granada, Granada, Spain
| | - José L Zugaza
- Department of Genetics, Physical Anthropology and Animal Physiology, University of the Basque Country, Leioa, Spain.,Achucarro Basque Center for Neuroscience, Bizkaia Science and Technology Park, Zamudio, Spain.,IKERBASQUE, Basque Foundation for Science, Bilbao, Spain
| | - Patricia Gálvez-Martín
- Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Granada, Granada, Spain.,R&D Human Health, Bioibérica S.A.U., Barcelona, Spain
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Functional expression of ZNF467 and PCBP2 supports adipogenic lineage commitment in adipose-derived mesenchymal stem cells. Gene 2020; 737:144437. [PMID: 32032745 DOI: 10.1016/j.gene.2020.144437] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2020] [Accepted: 02/03/2020] [Indexed: 01/13/2023]
Abstract
Bone marrow-derived mesenchymal stromal/stem cells (BMSCs) have the potential to be employed in many different skeletal therapies. A major limitation to utilizing BMSCs as a therapeutic strategy in human disease and tissue regeneration is the low cell numbers obtained from initial isolation necessitating multiple cell passages that can lead to decreased cell quality. Adipose-derived mesenchymal stromal/stem cells (AMSCs) have been proposed as an alternative cell source for regenerative therapies; however the differentiation capacity of these cells differs from BMSCs. To understand the differences between BMSCs and AMSCs, we compared the global gene expression profiles of BMSCs and AMSCs and identified two genes, PCBP2 and ZNF467 that were differentially expressed between AMSCs and BMSCs. We demonstrate that PCBP2 and ZNF467 impact adipogenic but not osteogenic differentiation, further supporting evidence that AMSCs and BMSCs appear to be adapted to their microenvironment.
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