S-SDF-1诱导免疫微环境促Sox10+神经嵴干细胞原位血管再生机制研究

小口径人工血管临床需求大，但远期通畅率低导致临床应用受到限制。近年来，原位组织工程技术试图通过招募内源性干细胞诱导血管再生，但因血管支架材料生物活性欠佳、炎性反应明显，影响管壁重构，且招募干细胞来源和命运不明。免疫调节生物材料成为组织工程当前研究的热点，本研究以改性生物材料构建诱导组织再生的免疫微环境为基础，拟将体内耐酶解S-SDF-1(S4V)结合至可降解血管支架，调控局部免疫微环境，通过mTORC2信号通路促进T淋巴细胞发生极化效应，Th2细胞数量和比例上调，从而招募Sox10+神经嵴干细胞参与血管再生，同时明确内源性Sox10+神经嵴干细胞来源及命运，为推进小口径组织工程血管再生机制研究和临床转化提供依据。

There is a critical clinical need for small-diameter vascular grafts. Currently used small-diameter vascular grafts have a poor long-term performance, limiting their utility and success. Recently recruiting endogenous stem cells for in situ blood vessel regeneration is a novel and efficient approach in vascular tissue engineering. However, the negative remodeling of the grafts are observed due to the poor bioactivity of the scaffolds and the pro-inflammatory effects of inflammatory cells on the recruitment, and the source and differentiation fate of the recruited cells are not determined. Biomaterial-based immunomodulation strategies are becoming the hot topic of tissue engineering. Therefore, we will investigate how the microfibrous scaffolds treated with a protease-resistant form of SDF-1, i.e., S-SDF-1(S4V), shape the immune microenvironment to improve the vascular regeneration. The scaffolds will induce a pro-regenerative response, characterized by increasing the population and proportion of T helper 2 cells regulated by an mTORC2 pathway that recruites Sox10+ neural crest stem cells, which is critical for functional vascular regeneration. And the source and differentiation fate of the recruited cells will be investigated using the lineage tracing. These results will provide a rational basis for better vascular graft development and clinical translation.