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      Hair follicle mesenchymal stem cell exosomal lncRNA H19 inhibited NLRP3 pyroptosis to promote diabetic mouse skin wound healing

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          Abstract

          Skin wounds caused by diabetes are a major medical problem. Mesenchymal stem cell-derived exosomes hold promise to quicken wound healing due to their ability to transfer certain molecules to target cells, including mRNAs, microRNAs, lncRNAs, and proteins. Nonetheless, the specific mechanisms underlying this impact are not elucidated. Therefore, this research aimed to investigate the effect of MSC-derived exosomes comprising long non-coding RNA (lncRNA) H19 on diabetic skin wound healing. Hair follicle mesenchymal stem cells (HF-MSCs) were effectively isolated and detected, and exosomes (Exo) were also isolated smoothly. Pretreatment with 30 mM glucose for 24 h (HG) could efficiently induce pyroptosis in HaCaT cells. Exosomal H19 enhanced HaCaT proliferation and migration and inhibited pyroptosis by reversing the stimulation of the NLRP3 inflammasome. Injection of exosomes overexpressing lncRNA H19 to diabetic skin wound promoted sustained skin wound healing, whereas sh-H19 exosomes did not have this effect. In conclusion, Exosomes overexpressing H19 promoted HaCaT proliferation, migration and suppressed pyroptosis both in vitro and in vivo. Therefore, HFMSC-derived exosomes that overexpress H19 may be included in strategies for healing diabetic skin wounds.

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          Most cited references51

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          Cutaneous wound healing.

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            Clinical Trials With Mesenchymal Stem Cells: An Update.

            In the last year, the promising features of mesenchymal stem cells (MSCs), including their regenerative properties and ability to differentiate into diverse cell lineages, have generated great interest among researchers whose work has offered intriguing perspectives on cell-based therapies for various diseases. Currently the most commonly used adult stem cells in regenerative medicine, MSCs, can be isolated from several tissues, exhibit a strong capacity for replication in vitro, and can differentiate into osteoblasts, chondrocytes, and adipocytes. However, heterogeneous procedures for isolating and cultivating MSCs among laboratories have prompted the International Society for Cellular Therapy (ISCT) to issue criteria for identifying unique populations of these cells. Consequently, the isolation of MSCs according to ISCT criteria has produced heterogeneous, nonclonal cultures of stromal cells containing stem cells with different multipotent properties, committed progenitors, and differentiated cells. Though the nature and functions of MSCs remain unclear, nonclonal stromal cultures obtained from bone marrow and other tissues currently serve as sources of putative MSCs for therapeutic purposes, and several findings underscore their effectiveness in treating different diseases. To date, 493 MSC-based clinical trials, either complete or ongoing, appear in the database of the US National Institutes of Health. In the present article, we provide a comprehensive review of MSC-based clinical trials conducted worldwide that scrutinizes biological properties of MSCs, elucidates recent clinical findings and clinical trial phases of investigation, highlights therapeutic effects of MSCs, and identifies principal criticisms of the use of these cells. In particular, we analyze clinical trials using MSCs for representative diseases, including hematological disease, graft-versus-host disease, organ transplantation, diabetes, inflammatory diseases, and diseases in the liver, kidney, and lung, as well as cardiovascular, bone and cartilage, neurological, and autoimmune diseases.
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              Literature review on the management of diabetic foot ulcer.

              Diabetic foot ulcer (DFU) is the most costly and devastating complication of diabetes mellitus, which affect 15% of diabetic patients during their lifetime. Based on National Institute for Health and Clinical Excellence strategies, early effective management of DFU can reduce the severity of complications such as preventable amputations and possible mortality, and also can improve overall quality of life. The management of DFU should be optimized by using a multidisciplinary team, due to a holistic approach to wound management is required. Based on studies, blood sugar control, wound debridement, advanced dressings and offloading modalities should always be a part of DFU management. Furthermore, surgery to heal chronic ulcer and prevent recurrence should be considered as an essential component of management in some cases. Also, hyperbaric oxygen therapy, electrical stimulation, negative pressure wound therapy, bio-engineered skin and growth factors could be used as adjunct therapies for rapid healing of DFU. So, it's suggested that with appropriate patient education encourages them to regular foot care in order to prevent DFU and its complications.
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                Author and article information

                Journal
                Aging (Albany NY)
                Aging
                Aging (Albany NY)
                Impact Journals
                1945-4589
                14 February 2023
                14 February 2023
                : 15
                : 3
                : 791-809
                Affiliations
                [1 ]Department of Cardiology, China-Japan Union Hospital of Jilin University, Changchun 130031, China
                [2 ]School of Public Health, Beihua University, Jilin 132033, China
                [3 ]College of Basic Medicine, Beihua University, Jilin 132033, China
                [4 ]Department of Laboratory Animal Science, China Medical University, Shenyang 110122, China
                Author notes
                Correspondence to: Chun Yang; email: yangchun1949@163.com, https://orcid.org/0000-0002-2195-5274
                Article
                204513 204513
                10.18632/aging.204513
                9970314
                36787444
                86be3e18-5050-42b9-91ec-c9c82fc4b72e
                Copyright: © 2023 Yang et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 30 May 2022
                : 02 February 2023
                Categories
                Research Paper

                Cell biology
                hfmscs,exosomes,lncrna h19,diabetes,skin wound healing
                Cell biology
                hfmscs, exosomes, lncrna h19, diabetes, skin wound healing

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