目的:在这项研究中,我们旨在确定人尿源干细胞(USC)和转基因USC的影响,这些细胞被设计为过度表达生肌生长因子IGF1(USCIGF),心脏毒素(CTX)损伤的小鼠骨骼肌的再生能力。
方法:我们在USC中过表达IGF1,并研究了心肌毒素损伤肌肉组织的成肌能力和再生功能的改变。
结果:与单独的USC相比,USCIGF1激活IGF1-Akt-mTOR信号通路,显著提高体外成肌分化能力,增强了生肌生长因子和细胞因子的分泌。此外,IGF1过表达增加了USC与骨骼肌细胞融合形成肌管的能力,调节促再生免疫反应和炎症细胞因子,在骨骼肌损伤的体内模型中,肌生成增加。
结论:总体而言,USC基因修饰过表达IGF1通过调节肌源性分化显着增强骨骼肌再生,旁分泌效应,和细胞融合,以及通过调节体内受伤骨骼肌的免疫反应。这项研究为评估USC作为骨骼肌生成中的非肌源性细胞来源的肌源性功能提供了新的视角。USC和IGF1表达的组合有可能为尿失禁患者的骨骼肌损伤和相关肌肉缺陷提供新的有效疗法。
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.
CONCLUSIONS: 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.