Regenerative Therapy最新文献

{"title":"Human resources required in the field of regenerative medicine: A follow-up of the Japanese survey in 2015","authors":"","doi":"10.1016/j.reth.2024.07.003","DOIUrl":"10.1016/j.reth.2024.07.003","url":null,"abstract":"<div><p>In 2015, we conducted a survey of the corporate members of FIRM on the human resources and training required in the field of regenerative cell therapies and reported the results in this journal. After that, industrialization of regenerative medicine has progressed and some cell products have been approved, and infrastructures, such as laws and educational systems, have been improved. To capture the changing demands for human resources in response to the shift in social circumstances, we conducted another survey. Consequently, now, there is an increasing demand for highly specialized skills and knowledge in the field of regenerative medicine. Furthermore, it was found that QA/QC managers and specialists of pharmaceutical affairs are strongly demanded, rather than technicians of cell culture. In addition, it became evident that there are still relatively few companies that have established their own internal education systems, and, in most cases, employees are trained by senior stuff. The establishment of efficient education systems in public institutions and academic societies is desired.</p></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352320424001317/pdfft?md5=0da04e905124a28c6bc48e234c0fa593&pid=1-s2.0-S2352320424001317-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141950280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Generation of in vivo-like multicellular liver organoids by mimicking developmental processes: A review","authors":"Ayumu Okumura,&nbsp;Kenji Aoshima,&nbsp;Naoki Tanimizu","doi":"10.1016/j.reth.2024.05.020","DOIUrl":"https://doi.org/10.1016/j.reth.2024.05.020","url":null,"abstract":"<div><p>Liver is involved in metabolic reactions, ammonia detoxification, and immunity. Multicellular liver tissue cultures are more desirable for drug screening, disease modeling, and researching transplantation therapy, than hepatocytes monocultures. Hepatocytes monocultures are not stable for long. Further, hepatocyte-like cells induced from pluripotent stem cells and <em>in vivo</em> hepatocytes are functionally dissimilar. Organoid technology circumvents these issues by generating functional <em>ex vivo</em> liver tissue from intrinsic liver progenitor cells and extrinsic stem cells, including pluripotent stem cells. To function as <em>in vivo</em> liver tissue, the liver organoid cells must be arranged precisely in the 3-dimensional space, closely mimicking <em>in vivo</em> liver tissue. Moreover, for long term functioning, liver organoids must be appropriately vascularized and in contact with neighboring epithelial tissues (e.g., bile canaliculi and intrahepatic bile duct, or intrahepatic and extrahepatic bile ducts). Recent discoveries in liver developmental biology allows one to successfully induce liver component cells and generate organoids. Thus, here, in this review, we summarize the current state of knowledge on liver development with a focus on its application in generating different liver organoids. We also cover the future prospects in creating (functionally and structurally) <em>in vivo</em>-like liver organoids using the current knowledge on liver development.</p></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S235232042400107X/pdfft?md5=70e5984d630283fd1a9ee2c94e40da43&pid=1-s2.0-S235232042400107X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141294770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing the wound healing process through local injection of exosomes derived from blood serum: An in vitro and in vivo assessment","authors":"Mehdi Rasti ,&nbsp;Amir Hossein Parniaei ,&nbsp;Leila Dehghani ,&nbsp;Salar Nasr Esfahani ,&nbsp;Hossein Mirhendi ,&nbsp;Vida Yazdani ,&nbsp;Vajihe Azimian Zavareh","doi":"10.1016/j.reth.2024.06.004","DOIUrl":"https://doi.org/10.1016/j.reth.2024.06.004","url":null,"abstract":"<div><h3>Introduction</h3><p>The skin plays a crucial role as a protective barrier against external factors, but disruptions to its integrity can lead to wound formation and hinder the natural healing process. Scar formation and delayed wound healing present significant challenges in skin injury treatment. While alternative approaches such as skin substitutes and tissue engineering exist, they are often limited in accessibility and cost. Exosomes have emerged as a potential solution for wound healing due to their regenerative properties.</p></div><div><h3>Methods</h3><p>In this study, exosomes were isolated from human blood serum using a kit. The exosomes were characterized, and their effects on cell migration were assessed <em>in vitro</em>. Additionally, the wound healing capacity of exosomes was evaluated <em>in vivo</em> using a rat full-thickness wound model.</p></div><div><h3>Results</h3><p>Our <em>in vitro</em> findings revealed that exosomes significantly promoted cell migration. <em>In vivo</em> experiments demonstrated that the injection of exosomes at different areas of the wound accelerated the wound healing process, resulting in wound closure, collagen synthesis, vessel formation, and angiogenesis in the wound area. These results suggest that exosomes have a promising therapeutic potential for expediting wound healing and minimizing scar formation.</p></div><div><h3>Conclusions</h3><p>The findings of this study highlight the potential of exosomes as a novel approach for enhancing wound healing. Exosomes showed positive effects on both cell migration and wound closure in <em>in vitro</em> and <em>in vivo</em> studies, suggesting their potential use as a regenerative therapy for skin injuries. Further research is needed to fully understand the mechanisms underlying the beneficial effects of exosomes on wound healing and to optimize their application in clinical settings.</p></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352320424001123/pdfft?md5=067684090080373533843008cae53cd7&pid=1-s2.0-S2352320424001123-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141423553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fortified electrospun collagen utilizing biocompatible Poly Glycerol Sebacate prepolymer (PGSp) and zink oxide nanoparticles (ZnO NPs) for diabetics wound healing: Physical, biological and animal studies","authors":"Ghazaleh Larijani ,&nbsp;Kazem Parivar ,&nbsp;Nasim Hayati Roodbari ,&nbsp;Parichehr Yaghmaei ,&nbsp;Naser Amini","doi":"10.1016/j.reth.2024.05.009","DOIUrl":"10.1016/j.reth.2024.05.009","url":null,"abstract":"<div><p>Collagen, a naturally occurring fibrous protein, is a potential resource of biological materials for tissue engineering and regenerative medicine because it is structurally biocompatible, has low immunogenicity, is biodegradable, and is biomimetic. Numerous studies have documented in the literature how Collagen nanofibers exhibit limited cell adhesion, poor viscosity, and no interior fibril structure. The biomedical industry is using Poly Glycerol Sebacate prepolymer(PGSp), a biodegradable and biocompatible polyester with high adhesion and very viscous appearance, more often. Here, unique electrospun Collagen/PGSp/ZnO/NPs blend nanofibers for skin tissue application were developed and described with varied PGSp percent. Additionally, when ternary blends of Collagen, PGSp, and Zink Oxide Nanoparticles (ZnO NPs) are used, the antibacterial properties of the scaffolds are improved. The bead-free electrospun nanofibers were produced by raising the PGSp concentration to 30%w/w. SEM, EDS, tensile, MTT, FTIR, SDS-page, swelling test, contact-angle, antimicrobial, biodegradation, XRD, and cell attachment procedures were used to characterize the crosslinked nanofibers. The ternary blend nanofibers with a weight ratio of Collagen/PGSp 30%/ZnONPs 1% had higher stress/strain strength (0.25 mm/mm), porosity (563), cell survival, and degradation time. Moreover, after applying for wound healing in diabetic rats, Collagen/PGSp 30%/could be show improving wound healing significantly compared to other groups.</p></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352320424000968/pdfft?md5=9b78e6af29264066f337a54ec8931da3&pid=1-s2.0-S2352320424000968-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141231049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel role of CD73-IFNγ signalling axis in human mesenchymal stromal cell mediated inflammatory macrophage suppression","authors":"Shashank Chandanala,&nbsp;Govind Mohan,&nbsp;David-Luther Manukonda,&nbsp;Anujith Kumar,&nbsp;Jyothi Prasanna","doi":"10.1016/j.reth.2024.05.011","DOIUrl":"10.1016/j.reth.2024.05.011","url":null,"abstract":"<div><h3>Introduction</h3><p>Immunomodulation is the predominant mechanism via which Mesenchymal stromal cells (MSCs) mediate their therapeutic benefits. However, inconsistent success in numerous clinical trials warrants a better understating of the molecular mechanisms regulating their immunomodulatory properties. CD73, an ecto-5′-nucleotidase is abundantly expressed by MSCs, however its precise role in regulating their immunomodulatory properties is still elusive. The present study explored the role of CD73 in Interferon-gamma (IFNγ) sensing and in turn their ability to suppress “inflammatory” M1 macrophages.</p></div><div><h3>Materials and methods</h3><p>CD73 knockdown MSCs (CD73-KDN) were initially assessed for expression of immunoregulatory molecules and IFNγ sensing ability by analysing expression of IFNγ signalling downstream targets such as pSTAT-1, Interferon-Stimulated Genes (ISG) and Indoleamine 2,3-dioxygnease (IDO), a prototypic IFNγ-induced immunomodulator. Next CD73-KDN MSCs were co-cultured with inflammatory M1 macrophages and evaluated for their ability to suppress them. To delineate the contributory role of CD73 and IFNγ signalling downstream target IDO, they were overexpressed independently in CD73-KDN MSCs and re-evaluated for their ability to suppress M1 macrophages.</p></div><div><h3>Results</h3><p>CD73-KDN MSCs exhibited reduced expression of immunoregulatory molecules and were refractory to IFNγ signalling as indicated by attenuated expression of pSTAT-1, Interferon-Stimulated Genes (ISG) and Indoleamine 2,3-dioxygnease (IDO) upon IFNγ exposure. Since sensing of inflammation is critical for MSC mediated immunomodulation, CD73-KDN MSCs were functionally evaluated for their ability to immune-modulate “inflammatory” M1 macrophages wherein they failed to suppress M1 macrophages. Interestingly, ectopic expression of either CD73 or IFNγ signalling target IDO1 in CD73-KDN MSCs restored their ability to suppress M1 macrophages, establishing the importance of CD73-IFNγ signalling axis in MSC-mediated inflammatory macrophage suppression.</p></div><div><h3>Conclusion</h3><p>The present study uncovers the unexplored role of CD73-IFNγ axis in MSC-mediated M1 macrophage suppression. MSC-educated macrophages are the actual immune-modulators at MSC transplant sites, thus CD73 can serve as a key immune-potency marker for benchmarking therapeutically relevant MSCs.</p></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S235232042400097X/pdfft?md5=6168362cb8fd0b6afca7b553284f90cb&pid=1-s2.0-S235232042400097X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141234501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel scaffold-free mesenchymal stem cell-derived tissue engineered construct for articular cartilage restoration - From basic to clinic","authors":"Kazunori Shimomura ,&nbsp;Wataru Ando ,&nbsp;David A. Hart ,&nbsp;Norimasa Nakamura","doi":"10.1016/j.reth.2024.05.007","DOIUrl":"10.1016/j.reth.2024.05.007","url":null,"abstract":"<div><p>Treatments for articular cartilage injuries are still challenging, due in part to its avascular and aneural surroundings. Since the first report of autologous chondrocyte implantation, cell-based therapies have been extensively studied with a variety of cell sources, including chondrocytes and mesenchymal stem/stromal cells (MSCs). Recently, MSC-based therapy has received considerable research attention because of the relative ease in handling for tissue harvest, and subsequent cell expansion and differentiation. Using such cells, we have originally developed a 3-dimensional scaffold-free tissue-engineered construct (TEC) through simple-cell culture methods and demonstrated its feasibility for cartilage repair and regeneration in the first-in-human clinical trial. This review summarizes our novel scaffold-free approaches to use MSC for the restoration of damaged articular cartilage, documenting the progression from basic to clinical studies.</p></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352320424000944/pdfft?md5=edd4baa30aa1da225e81f34120f658cf&pid=1-s2.0-S2352320424000944-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141233880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring calcium-free alternatives in endochondral bone repair tested on In vivo trials - A review","authors":"William Cárdenas-Aguazaco,&nbsp;Adriana Lorena Lara-Bertrand,&nbsp;Leonardo Prieto-Abello,&nbsp;Nicolás Barreto-López,&nbsp;Bernardo Camacho,&nbsp;Ingrid Silva-Cote","doi":"10.1016/j.reth.2024.05.017","DOIUrl":"https://doi.org/10.1016/j.reth.2024.05.017","url":null,"abstract":"<div><p>Bone repair via endochondral ossification is a complex process for the critical size reparation of bone defects. Tissue engineering strategies are being developed as alternative treatments to autografts or allografts. Most approaches to bone regeneration involve the use of calcium composites. However, exploring calcium-free alternatives in endochondral bone repair has emerged as a promising way to contribute to bone healing. By analyzing researches from the last ten years, this review identifies the potential benefits of such alternatives compared to traditional calcium-based approaches. Understanding the impact of calcium-free alternatives on endochondral bone repair can have profound implications for orthopedic and regenerative medicine. This review evaluates the efficacy of calcium-free alternatives in endochondral bone repair through <em>in vivo</em> trials. The findings may guide future research to develop innovative strategies to improve endochondral bone repair without relying on calcium. Exploring alternative approaches may lead to the discovery of novel therapies that improve bone healing outcomes.</p></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352320424001044/pdfft?md5=1cecf4fd8849e6344c21b2da6e07a11e&pid=1-s2.0-S2352320424001044-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141240887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel cell therapy with ex vivo cultured peripheral blood mononuclear cells significantly impacts angiogenesis in the murine ischemic limb model","authors":"Satomi Furukawa ,&nbsp;Rie Hirano ,&nbsp;Ai Sugawara ,&nbsp;Satoshi Fujimura ,&nbsp;Rica Tanaka","doi":"10.1016/j.reth.2024.06.009","DOIUrl":"https://doi.org/10.1016/j.reth.2024.06.009","url":null,"abstract":"<div><h3>Introduction</h3><p>Autologous mononuclear cells (MNCs) have been used in vascular regenerative therapy since the identification of endothelial progenitor cells (EPCs). However, the efficacy of autologous EPC therapy for diseases such as diabetes and connective tissue disorders is limited due to deficiencies in the number and function of EPCs. To address this, we developed a novel RE-01 cells that enriches pro-angiogenic cells from peripheral blood MNCs (PBMNCs).</p></div><div><h3>Methods</h3><p>PBMNCs were collected from healthy volunteers following ethical guidelines. RE-01 cells were cultured in the presence of specific growth factors for 5 days without media change. Flow cytometry was used to analyze cell surface markers. Tube formation assays, EPC culture assays, and mRNA analysis were performed to evaluate angiogenic potential. The efficacy of RE-01 cells upon transplantation into ischemic hind limbs of mice was evaluated.</p></div><div><h3>Results</h3><p>RE-01 cells exhibited a significant increase in pro-angiogenic cells such as M2 macrophages and angiogenic T cells, in contrast to PBMNCs, while the number of inflammatory cells reduced. <em>In vitro</em> assays demonstrated the enhanced angiogenic abilities of RE-01 cells, supported by increased mRNA expression of angiogenesis-related cytokines. <em>In vivo</em> studies using mouse ischemic hind limb models have shown that blood flow and angiogenesis improved following RE-01 cell transplantation. Transplantations for 3 consecutive days significantly improved the number of pericyte-recruited vessels in the severely ischemic hind limbs of mice.</p></div><div><h3>Conclusions</h3><p>RE-01 cells showed promising results in enhancing angiogenesis and arteriogenesis, possibly owing to the presence of M2 macrophages and angiogenic T cells. These cells also demonstrated anti-fibrotic effects. The efficacy of RE-01 cells has been confirmed in mouse models, suggesting their potential for treating ischemic vascular diseases. Clinical trials are planned to validate the safety and efficacy of RE-01 cell therapy in patients with connective tissue disease and unhealed ulcers. We hope that this new RE-01 cell therapy will prevent many patients from undergoing amputation.</p></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352320424001159/pdfft?md5=f81c17933c92e9c6bd16f02f88f6caf8&pid=1-s2.0-S2352320424001159-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141434277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical application of platelet rich plasma to promote healing of open hand injury with skin defect","authors":"Xinhui Du ,&nbsp;Jiarui Zhao ,&nbsp;Qian Ren ,&nbsp;Yibo Ma ,&nbsp;Pengxia Duan ,&nbsp;Yansheng Huang ,&nbsp;Sibo Wang","doi":"10.1016/j.reth.2024.06.003","DOIUrl":"https://doi.org/10.1016/j.reth.2024.06.003","url":null,"abstract":"<div><h3>Background</h3><p>Skin defects caused by open hand trauma are difficult to treat clinically and severely affect the recovery of hand function. Autologous platelet-rich plasma (PRP) has been widely used in the treatment of refractory chronic wounds, but its use in hand trauma skin defects remains scarce.</p></div><div><h3>Methods</h3><p>This study compared the outcomes of 27 patients treated with PRP to 31 patients undergoing skin flap transplantation for hand wounds. We assessed several parameters, including healing times, duration of surgery, postoperative pain (VAS score), intraoperative amputation length, finger function, sensation restoration, nail bed preservation, and hospitalization expenses.</p></div><div><h3>Results</h3><p>PRP-treated patients showed a mean healing time of 21.59 ± 3.17 days. Surgical times were significantly shorter in the PRP group (22.04 ± 7.04 min) compared to the flap group (57.45 ± 8.15 min, P &lt; 0.0001). PRP patients experienced longer postoperative healing times (20.15 ± 2.16 days) than those in the skin flap group (12.84 ± 1.08 days, P &lt; 0.0001), but reported lower pain scores (1.3 ± 1.44 vs 2.55 ± 2.06, P = 0.0119). Range of Motion (ROM) at the proximal interphalangeal joint was better in the PRP group (96.26° ± 6.69) compared to the flap group (86.16° ± 15.24, P = 0.0028). Sensory outcomes favored the PRP group, with a two-point discrimination of 2.37 ± 1.34 mm versus 2.52 ± 1.27 mm in the flap group (P = 0.0274). Costs were lower in the PRP group ($2081.6 ± 258.14 vs $2680.18 ± 481.15, P &lt; 0.0001).</p></div><div><h3>Conclusion</h3><p>PRP treatment for skin defects from hand trauma is effective, offering advantages in terms of reduced surgical time, pain, and cost, with comparable or superior functional outcomes to flap transplantation. Despite longer healing times, PRP may represent a preferable option for open hand injuries, preserving more nail beds and resulting in better sensation and joint motion.</p></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S235232042400110X/pdfft?md5=5bc3b69dbcb9bb6ee64bdf2d829fab81&pid=1-s2.0-S235232042400110X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141438956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NSUN2 facilitates tenogenic differentiation of rat tendon-derived stem cells via m5C methylation of KLF2","authors":"","doi":"10.1016/j.reth.2024.08.023","DOIUrl":"10.1016/j.reth.2024.08.023","url":null,"abstract":"<div><h3>Introduction</h3><p>Tendon-derived stem cells (TDSCs) play a critical role in tendon repair. N5-methylcytosine (m5C) is a key regulator of cellular processes such as differentiation. This study aimed to investigate the impact of m5C on TDSC differentiation and the underlying mechanism.</p></div><div><h3>Methods</h3><p>TDSCs were isolated from rats and identified, and a tendon injury rat model was generated. Tenogenic differentiation <em>in vitro</em> was evaluated using Sirius red staining and quantitative real-time polymerase chain reaction, while that <em>in vivo</em> was assessed using immunohistochemistry and hematoxylin‒eosin staining. m5C methylation was analyzed using methylated RNA immunoprecipitation, dual-luciferase reporter assay, and RNA stability assay.</p></div><div><h3>Results</h3><p>The results showed that m5C levels and NSUN2 expression were increased in TDSCs after tenogenic differentiation. Knockdown of NSUN2 inhibited m5C methylation of KLF2 and decreased its stability, which was recognized by YBX1. Moreover, interfering with KLF2 suppressed tenogenic differentiation of TDSCs, which could be abrogated by KLF2 overexpression. Additionally, TDSCs after NSUN2 overexpression contributed to ameliorating tendon injury <em>in vivo</em>. In conclusion, NSUN2 promotes tenogenic differentiation of TDSCs via m5C methylation of KLF2 and accelerates tendon repair.</p></div><div><h3>Conclusions</h3><p>The findings suggest that overexpression of NSUN2 can stimulate the differentiation ability of TDSCs, which can be used in the treatment of tendinopathy.</p></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352320424001585/pdfft?md5=0180a9ed582631d2e1bc71dcb63bdf7d&pid=1-s2.0-S2352320424001585-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142168508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}