Hualin Yi, Gang Chen, Shuai Qiu, Joshua T Maxwell, Guiting Lin, Tracy Criswell, Yuanyuan Zhang
{"title":"经 IGF1 基因修饰的尿源干细胞可改善肌肉再生。","authors":"Hualin Yi, Gang Chen, Shuai Qiu, Joshua T Maxwell, Guiting Lin, Tracy Criswell, Yuanyuan Zhang","doi":"10.62347/QSKH2686","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>In this study we aimed to determine the impact of human urine derived stem cells (USC) and genetically modified USC that were designed to overexpress myogenic growth factor IGF1 (USC<sup>IGF</sup>), on the regenerative capacity of cardiotoxin (CTX)-injured murine skeletal muscle.</p><p><strong>Methods: </strong>We overexpressed IGF1 in USC and investigated the alterations in myogenic capacity and regenerative function in cardiotoxin-injured muscle tissues.</p><p><strong>Results: </strong>Compared with USC alone, USC<sup>IGF1</sup> activated the IGF1-Akt-mTOR signaling pathway, significantly improved myogenic differentiation capacity in vitro, and enhanced the secretion of myogenic growth factors and cytokines. In addition, IGF1 overexpression increased the ability of USC to fuse with skeletal myocytes to form myotubes, regulated the pro-regenerative immune response and inflammatory cytokines, and increased myogenesis in an in vivo model of skeletal muscle injury.</p><p><strong>Conclusion: </strong>Overall, USC genetically modified to overexpress IGF1 significantly enhanced skeletal muscle regeneration by regulating myogenic differentiation, paracrine effects, and cell fusion, as well as by modulating immune responses in injured skeletal muscles in vivo. This study provides a novel perspective for evaluating the myogenic function of USC as a nonmyogenic cell source in skeletal myogenesis. The combination of USC and IGF1 expression has the potential to provide a novel efficient therapy for skeletal muscle injury and associated muscular defects in patients with urinary incontinence.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":null,"pages":null},"PeriodicalIF":1.5000,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11087207/pdf/","citationCount":"0","resultStr":"{\"title\":\"Urine-derived stem cells genetically modified with IGF1 improve muscle regeneration.\",\"authors\":\"Hualin Yi, Gang Chen, Shuai Qiu, Joshua T Maxwell, Guiting Lin, Tracy Criswell, Yuanyuan Zhang\",\"doi\":\"10.62347/QSKH2686\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>In this study we aimed to determine the impact of human urine derived stem cells (USC) and genetically modified USC that were designed to overexpress myogenic growth factor IGF1 (USC<sup>IGF</sup>), on the regenerative capacity of cardiotoxin (CTX)-injured murine skeletal muscle.</p><p><strong>Methods: </strong>We overexpressed IGF1 in USC and investigated the alterations in myogenic capacity and regenerative function in cardiotoxin-injured muscle tissues.</p><p><strong>Results: </strong>Compared with USC alone, USC<sup>IGF1</sup> activated the IGF1-Akt-mTOR signaling pathway, significantly improved myogenic differentiation capacity in vitro, and enhanced the secretion of myogenic growth factors and cytokines. In addition, IGF1 overexpression increased the ability of USC to fuse with skeletal myocytes to form myotubes, regulated the pro-regenerative immune response and inflammatory cytokines, and increased myogenesis in an in vivo model of skeletal muscle injury.</p><p><strong>Conclusion: </strong>Overall, USC genetically modified to overexpress IGF1 significantly enhanced skeletal muscle regeneration by regulating myogenic differentiation, paracrine effects, and cell fusion, as well as by modulating immune responses in injured skeletal muscles in vivo. This study provides a novel perspective for evaluating the myogenic function of USC as a nonmyogenic cell source in skeletal myogenesis. The combination of USC and IGF1 expression has the potential to provide a novel efficient therapy for skeletal muscle injury and associated muscular defects in patients with urinary incontinence.</p>\",\"PeriodicalId\":7438,\"journal\":{\"name\":\"American journal of clinical and experimental urology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.5000,\"publicationDate\":\"2024-04-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11087207/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"American journal of clinical and experimental urology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.62347/QSKH2686\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q3\",\"JCRName\":\"UROLOGY & NEPHROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"American journal of clinical and experimental urology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.62347/QSKH2686","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"UROLOGY & NEPHROLOGY","Score":null,"Total":0}
Urine-derived stem cells genetically modified with IGF1 improve muscle regeneration.
Objective: In this study we aimed to determine the impact of human urine derived stem cells (USC) and genetically modified USC that were designed to overexpress myogenic growth factor IGF1 (USCIGF), on the regenerative capacity of cardiotoxin (CTX)-injured murine skeletal muscle.
Methods: We overexpressed IGF1 in USC and investigated the alterations in myogenic capacity and regenerative function in cardiotoxin-injured muscle tissues.
Results: Compared with USC alone, USCIGF1 activated the IGF1-Akt-mTOR signaling pathway, significantly improved myogenic differentiation capacity in vitro, and enhanced the secretion of myogenic growth factors and cytokines. In addition, IGF1 overexpression increased the ability of USC to fuse with skeletal myocytes to form myotubes, regulated the pro-regenerative immune response and inflammatory cytokines, and increased myogenesis in an in vivo model of skeletal muscle injury.
Conclusion: Overall, USC genetically modified to overexpress IGF1 significantly enhanced skeletal muscle regeneration by regulating myogenic differentiation, paracrine effects, and cell fusion, as well as by modulating immune responses in injured skeletal muscles in vivo. This study provides a novel perspective for evaluating the myogenic function of USC as a nonmyogenic cell source in skeletal myogenesis. The combination of USC and IGF1 expression has the potential to provide a novel efficient therapy for skeletal muscle injury and associated muscular defects in patients with urinary incontinence.