严重下肢缺血性疾病，无论外科搭桥还是介入腔内成形治疗疗效均很差，大多数患者仍无法避免截肢。注射间充质干细胞(MSCs)促进下肢缺血部位血管新生、加强侧支循环建立是最具前景的治疗方式。但既往对干细胞向内皮细胞分化的分子机制研究甚少，所涉及的基因、信号通路和局部微环境尚不清楚，限制了干细胞治疗下肢缺血性疾病的临床广泛应用。我们前期筛选出在血管新生中发挥重要调节作用的新靶点LILRA2基因，将通过过表达和基因敲除在细胞和动物模型水平阐明其在体外及体内的成血管能力；研究其发挥调控血管新生的信号通路及对局部免疫微环境的影响；明确MSCs输入体内后的示踪问题。本研究将发现全新的血管生成调节基因，对于提高MSCs向内皮细胞定向诱导分化效率、增强分化后内皮细胞功能特性具有重要意义，同时进一步阐明免疫微环境与血管新生的关系，通过转化医学研究确定其临床转化的可能性，为下肢缺血性疾病提供潜在的有效的治疗新靶点。

For critical limb ischemia diseases, both surgical bypass and interventional endovascular plasty are ineffective, and amputation is still unavoidable in most patients. Injection of mesenchymal stem cells (MSCs) to promote angiogenesis and strengthen collateral circulation is the most promising treatment. However, little research has been done on the molecular mechanism of stem cells differentiation into endothelial cells in the past. The genes, signal pathways and local microenvironment involved are still unclear, which limits the wide clinical application of stem cells in the treatment of lower limb ischemic diseases. We screened out a new target gene LILRA2 which plays an important regulatory role in angiogenesis. We will elucidate its angiogenesis ability in vitro and in vivo at the level of cells and animal models through gene overexpression and gene knockout; study its signal pathway to regulate angiogenesis and its effect on local immune microenvironment; and clarify the tracing problem after MSCs are imported into vivo. This study will discover a new angiogenesis regulator gene, which is of great significance to improve the efficiency of directional differentiation of MSCs into endothelial cells and enhance the functional characteristics of endothelial cells. At the same time, the relationship between immune microenvironment and angiogenesis will be further clarified. The possibility of clinical transformation will be determined through translational medicine research. This research will provide a potential, effective and new treatment target for critical limb ischemia diseases.