人尿源性干细胞外泌体对糖尿病膀胱逼尿肌Cajal样间质细胞的调节作用及机制

膀胱功能障碍是糖尿病患者常见的泌尿系统并发症，发病机制复杂，治疗困难。膀胱逼尿肌中Cajal样间质细胞（ICCs）具有起搏细胞特征，对膀胱功能具有重要意义。高糖环境中膀胱逼尿肌ICCs数量减少、干细胞因子（SCF）/C-kit通路异常导致ICCs功能缺陷，可能是糖尿病膀胱（DCP）发病机制之一。研究提示人尿源性干细胞（USCs）具有广泛的泌尿系统治疗作用和治疗糖尿病并发症的良好潜力，而干细胞外泌体可以降低细胞移植致瘤风险。我们前期研究表明，DCP膀胱中ICCs数量明显减少，移植人尿源性干细胞外泌体（USCs-Exo）后DCP大鼠的膀胱功能得到明显改善。本项目拟在前期研究基础上探索USCs-Exo改善DCP膀胱功能的机制，通过细胞水平和动物水平进一步验证USCs-Exo对ICCs的调节作用及SCF/C-kit通路的变化，探索DCP新的治疗途径。

Bladder dysfunction is a common complication of urinary system in diabetic patients with complicated pathogenesis and difficult treatment. The interstitial cells of Cajal(ICCs) of bladder detrusor are of great significance to bladder function with pacemaker cell characteristics. The fewer number of detrusor ICCs in high glucose environment and the abnormality of stem cell factor(SCF)/C-kit pathway which leads to the functional defects of ICCs may be the important pathogenesis of diabetic cystopathy (DCP). Recent studies suggest that human urine-derived stem cells（USCs） have a wide range of urological therapeutic effects and good potential for the treatment of diabetic complications，while exosomes secreted by stem cells have lower oncogenic risk after transplantation compared to stem cells. Our previous studies showed that the number of ICCs in the bladder of DCP was significantly reduced. The bladder function of DCP rats after transplantation of exosomes secreted by human urine-derived stem cells(USCs-Exo) was greatly improved. On this basis, our study is aimed to analyze the mechanism of USCs-Exo improving DCP bladder function, investigate the regulatory role of USCs-Exo on ICCs and the changes of SCF/C-kit pathway through cell and animal level, and explore new ways for the treatment of DCP.