脐带间充质干细胞调节巨噬细胞极化治疗糖尿病的作用及分子机制研究

Umbilical cord mesenchymal stem cells (UCMSCs) are a novel strategy for the treatment of diabetes mellitus and its complications, but the mechanism is still unclear. Our research group initially found that the improvement of insulin resistance by transplantation of umbilical cord mesenchymal stem cells was related to macrophages in diabetic rats. Some studies have confirmed that macrophage polarization plays an important role in the repair of tissue damage. Scientific hypothesis of the mechanism of urinary disease. The aim of this study was to evaluate the long-term efficacy of umbilical cord mesenchymal stem cells (UCMSCs) on diabetes mellitus (DM) in beagle dogs and to observe the effect of UCMSCs on M1/M2 polarization of macrophages. Finally, the non-contact co-culture model in vitro was used to further verify the possibility of UCMSCs passing COX-2 and/or TSG-6. Signal pathway inhibits the expression of TNF-alpha in macrophages, inhibits the activation of inflammatory bodies of NLRP3, reduces the release of IL-1beta, and plays a therapeutic role in diabetes mellitus. This study will elucidate the possible molecular mechanism of umbilical cord mesenchymal stem cells regulating macrophage polarization, and provide a scientific basis for clinical use of umbilical cord mesenchymal stem cells in the treatment of diabetes mellitus.

脐带间充质干细胞是治疗糖尿病及并发症的一种新兴策略，但其作用机制尚不清楚。课题组在前期初步发现移植脐带间充质干细胞对糖尿病大鼠胰岛素抵抗的改善作用与巨噬细胞有关，有研究证实巨噬细胞极化在组织损伤修复中发挥着重要作用，为此，本课题组提出脐带间充质干细胞调节巨噬细胞极化治疗糖尿病的作用机制的科学假说。本项目拟通过糖尿病Beagle犬大动物模型，评价脐带间充质干细胞对糖尿病的长期疗效，并观察脐带间充质干细胞对巨噬细胞M1/M2极化的影响；最后利用体外非接触共培养模型，进一步验证脐带间充质干细胞可能通过COX-2和/或TSG-6信号通路，抑制巨噬细胞TNF-α的表达，并抑制NLRP3炎症小体活化，减少IL-1β的释放，发挥对糖尿病的治疗作用。本研究将阐明脐带间充质干细胞调节巨噬细胞极化可能存在的分子机制，为临床使用脐带间充质干细胞治疗糖尿病提供科学理论依据。

间充质干细胞是治疗糖尿病及并发症的一种新兴策略，但其作用机制尚不清楚。本项目建立了一种不含血清、不含动物源成份、所有成份非常明确的扩增系统，进行脐带间充质干细胞（UCMSCs）的生物学特性、安全性、生物效能和质量检测，建立了临床级UCMSCs制剂；进一步通过糖尿病大鼠模型，证实了UCMSCs对糖尿病有较好的治疗效果，并初步发现移植UCMSCs对糖尿病大鼠胰岛素抵抗的改善作用与巨噬细胞M1/M2极化有关，并通过分子生物学技术筛选出间充质干细胞调控巨噬细胞极化关键分子，阐明其可能存在的分子机制。本研究为临床使用UCMSCs治疗糖尿病提供科学理论依据。