间充质干细胞及其联合生物材料支架在宫腔粘连治疗中的应用

The Application of Mesenchymal Stem Cells and Combined Biomaterial Scaffolds in the Treatment of Intrauterine Adhesions

宫腔粘连(intrauterine adhesions,IUA)是导致女性不孕症的首要子宫性因素,目前的治疗措施难以改善内膜再生情况,且极易复发。间充质干细胞(mesenchymal stem cells,MSCs)被广泛应用于再生医学研究,其来源包括骨髓、脐带、羊膜、脂肪和经血等。许多研究证明不同来源的MSCs均可抑制子宫内膜纤维化、促进内膜损伤修复,提示MSCs可应用于治疗IUA的研究。其机制主要涉及MSCs的3种功能:旁分泌、免疫调节以及直接分化为子宫内膜细胞。但MSCs的体外存活率和利用率较低,且全身及局部单独使用MSCs均难以长期存留。生物材料支架可负载MSCs以构建原位递送系统,宫内灌注后可延长MSCs存留时间。目前常用的生物材料包括透明质酸、胶原蛋白、温敏性水凝胶及其他材料。部分生物材料支架还可以改善MSCs特性,增强其趋化和分泌能力,提高疗效。综述MSCs及其联合生物材料支架在IUA治疗的临床研究中的应用。

Intrauterine adhesions(IUA)is the primary uterine factor contributing to female infertility,and current therapeutic measures are difficult to improve endometrial regeneration with a high risk of recurrence.Mesenchymal stem cells(MSCs)have been widely used in regenerative medicine research,and the sources of MSCs include bone marrow,umbilical cord,amniotic membrane,adipose,and menstrual blood.Numerous studies demonstrated that MSCs may inhibit endometrial fibrosis,promote endometrial repair,suggesting that MSCs can be used to treat IUA in clinical study.The mechanisms involve three main functions of MSCs:paracrine,immunomodulatory and direct differentiation into endometrial cells.However,the in vitro survivability and utilization rate of MSCs are low,and the long-term retention of MSCs is difficult for both systemic and local applications.Biomaterial scaffolds can be loaded with MSCs to build an in situ delivery system and prolong the retention time of MSCs after intrauterine perfusion.Commonly used biomaterials include hyaluronic acid,collagen,temperature-sensitive hydrogels and other materials.Some biomaterial scaffolds can even improve the properties of MSCs,enhance their chemotactic and secretory abilities,and improve the therapeutic efficacy.This article reviews the application of MSCs and the combined biomaterial scaffolds in the experimental treatment of IUA.