BIO促进脂肪来源干细胞修复急性心肌梗死的作用及机制

脂肪来源干细胞（ADSCs）因其来源丰富、自体可取、安全性好等，已成为治疗急性心肌梗死（AMI）最具应用前景的干细胞，但移植后存活率低已成为向临床转化的重要瓶颈，预处理提高ADSCs活性已成为研究热点。我们前期发现，小分子天然物质BIO可以促进ADSCs增殖、减轻H2O2诱导的损伤。在此基础上，本项目拟模拟AMI早期局部心肌微环境，进一步观察BIO预处理的ADSCs在长时间低氧状态下增殖、抗炎、抗凋亡、旁分泌能力的变化，以及对共培养H9c2细胞的作用，并探讨BIO提高ADSCs活性的机制。在体内，用BIO预处理的ADSCs移植治疗大鼠AMI，不同时相点活体成像示踪心脏内ADSCs，检测炎性细胞、旁分泌因子、血管密度、纤维化程度和心功能的变化。在治疗后7天对心脏组织进行单细胞测序，分析关键分子的基因表达，利用拟时序分析研究各种细胞的命运轨迹，揭示BIO预处理的ADSC治疗AMI的效果和机制。

Adipose derived stem cells (ADSCs) has become the most promising stem cells in the treatment of acute myocardial infarction (AMI) because of their abundant, autogenous sources and good security. However, its clinical application is significantly hampered by the low survival rate of engrafted cells, so pretreatment to improve ADSCs activity has become a research focus. Our preliminary data found that BIO, a small molecule natural substance, could promote proliferation and reduce H2O2-induced damage of ADSCs. In this project, in vitro, the proliferation, anti-inflammatory, anti-apoptosis and paracrine ability of BIO-pretreated ADSCs will be observed in long-term hypoxic culture condition simulating the local microenvironment in infarct heart, as well as the effect of pretreated ADSCs on co-cultured H9c2 cells will be studied, and the mechanism of BIO enhancing ADSCs viability will be explored further. In vivo, BIO-pretreated ADSCs will be transplanted into the heart of AMI rat, and traced with in vivo imaging at different phase points after transplantation, while the changes of inflammatory cells, paracrine factors, vascular density, degree of fibrosis and cardiac function will be examined. Single cell sequencing will be carried out for myocardial tissues in 7 days post-transplantation, the gene expression of key molecules will be investigated, and the fate tracks of various cells will be studied by pseudotime analysis, thus to reveal the effect and mechanisms of BIO pretreated-ADSCs transplantation for treatment of AMI.