目前基于间充质干细胞（MSCs）移植的治疗性血管新生是促进重度肢体缺血血流恢复和功能重建的重要手段，然而与外周血管疾病相关的糖尿病、高血压、动脉粥样硬化及衰老等因素严重影响骨髓MSCs（hBM-MSCs）的体内移植疗效。申请人前期发现人胚胎干细胞来源MSCs（hES-MSCs）与hBM-MSCs相比，来源稳定，无供体和批次差异，具备更强的治疗性血管新生潜能，且无致瘤风险。同时通过二代测序、功能学筛选及生物信息学预测，发现长非编码RNA RP11-262A16.1可能通过募集SWI/SNF调控NR2F2转录表达，进而调控hES-MSCs血管新生，而E2F1可能调控RP11-262A16.1转录表达。本项目拟在前期基础上，通过体内外实验，深入探讨E2F1/RP11-262A16.1/NR2F2环路在hES-MSCs发挥治疗性血管新生中的作用及机制，为促进缺血组织修复和功能重建提供重要借鉴。

At present, therapeutic angiogenesis based on mesenchymal stem cells (MSCs) transplantation is an important strategy to promote flow recovery and functional reconstruction of critical limb ischemia, but peripheral vascular disease associated diabetes, hypertension, atherosclerosis and aging seriously affect the therapeutic effects of bone marrow MSCs (hBM-MSCs). Based on previous studies, we found that, compared with hBM-MSCs, human embryonic stem cell derived MSCs (hES-MSCs) had a higher therapeutic angiogenesis potential without donor/batch differences and tumor risk. Additionally, through next generation sequencing, functional screening and bioinformatic prediction, we found that long noncoding RNA RP11-262A16.1 may recruit SWI/SNF to regulate NR2F2 transcription, thus regulating hES-MSCs angiogenesis, and E2F1 may regulate RP11-262A16.1 transcription. This project intends to explore the role and mechanism of E2F1/RP11-262A16.1/NR2F2 loop in the therapeutic angiogenesis of hES-MSCs through in vivo/vitro experiments, and provides important evidence for promoting the repair and functional reconstruction of ischemic tissue.