基因工程化绵羊肌源性干细胞生物补片的制备及在盆腔器官脱垂修复治疗中的应用

项目名称： 基因工程化绵羊肌源性干细胞生物补片的制备及在盆腔器官脱垂修复治疗中的应用

项目编号： No.81501238

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 李玢

作者单位： 西安交通大学

项目金额： 18万元

中文摘要： 传统手术及利用合成网片修复盆腔器官脱垂均为解剖学恢复，尚未达到组织修复，且易过度纤维化形成增生性瘢痕，其力学性能明显低于阴道正常组织，利用猪小肠粘膜下层基质（SIS）负载绵羊肌源性干细胞（MDSC），有望接近组织学修复，但MDSC在体外诱导分化过程中存在向肌成纤维细胞分化可能，将促进增生性瘢痕形成，Wnt/β-catenin通路与增生性瘢痕发生相关，因此本研究拟通过外源调控Wnt/β-catenin通路，观察共培养法MDSC定向分化过程中，肌成纤维细胞关键细胞标志物a-SMA和平滑肌分化晚期标志物Calponin表达变化情况，及细胞增殖和细胞周期改变，明确调控该通路促进共培养法MDSC向阴道平滑肌细胞定向分化及其抗瘢痕化的可行性，并通过体内外生物力学研究及组织学研究，明确调控Wnt/β-catenin通路抗瘢痕化与生物力学性能的相关性，为组织工程补片应用于临床提供理论依据

中文关键词： 盆腔器官脱垂；肌源性干细胞；Wnt信号通路；组织工程；生物力学特性

英文摘要： Traditional surgery and using synthetic mesh to repair pelvic organ prolapse are both anatomical restoration. They have not yet reached the tissue repair, and easily to form hypertrophic scars，which can cause hypertrophic scars and their mechanical properties are significantly lower than normal vaginal tissue. The use of pig small intestine submucosa matrix (SIS) to load sheep muscle-derived stem cells (MDSC) is expected to approach the vaginal tissue repair. But MDSC is possible to differentiate into myofibroblasts in the course of induced differentiation in vitro, which will promote the formation of hypertrophic scars. Wnt /β-catenin signaling pathway is invovled in hypertrophic scars. Therefore, this study is to observe the changes of the myofibroblasts key marker a-SMA and smooth muscle terminal differentiation markers Calponin, during the process of induced differentiation of the MDSC into vaginal smooth muscle cells by co-culture method. And observed the change of cell proliferation and cell cycle when regulating the Wnt /β-catenin signaling pathway, to explore the feasibility of regulating Wnt /β-catenin signaling pathway to promote sheep MDSC differentiation into vaginal smooth muscle cells and anti-scarring, in vitro. Through biomechanical and tissue engineering research both in vivo and in vitro to elucidate the correlation between anti-scarring effect and biomechanics changes through regulating Wnt /β-catenin signaling pathway，and to provide a theoretical basis for the clinical application of tissue engineering patch

英文关键词： Pelvic organ prolapse;Muscle-derived stem cells;Wnt signaling pathway; Tissue engineering;Biomechanics