成骨和改善血供是治疗股骨头坏死的理想方法。研究表明HIF1α可促进MSCs向成骨细胞分化以及EPCs归巢至缺血区，从而促进成骨和血管新生。但HIF1α易降解，导致其作用减弱。我们通过基因突变方法获得在常氧下不易降解的HIF1α，初步研究发现突变型 HIF1α修饰的MSCs产生含有促进血管新生的外泌体。因此假设，突变型HIF1α修饰MSCs后，除了促进MSCs向成骨细胞分化以及EPCs归巢外，产生的外泌体可增强骨坏死区血管新生。本研究拟通过细胞培养、免疫组化、免疫印迹、流式细胞分析和分选、动物实验等，证明通过突变型HIF1α修饰MSCs，不仅促进MSCs的成骨作用，而且促进EPCs归巢；并进一步探讨突变型HIF1α修饰的MSCs通过外泌体增强EPCs血管新生的机制，为股骨头坏死的治疗提供新途径。

Promoting osteogenesis and angiogenesis is an ideal method for the treatment of femoral head necrosis. Studies have shown that HIF1α can promote MSCs differentiating into osteoblast and EPCs homing to the ischemic area, thereby enhancing osteogenesis and angiogenesis. But HIF1α is easily biodegradable under normoxic condition, resulting in weakened effects of itself. We got non-degraded HIF1α under normoxic condition by gene mutation methods. Preliminary study found that mutant HIF1α modified MSCs produce exosomes that promote angiogenesis. Thus, we hypothesize,in addition to promoting osteoblastic differentiation of MSCs and homing of EPCs to the ischemic site, mutant HIF1α modified MSCs produce exosomes which can enhance angiogenesis in necrotic area of bone. By cell culture, immunohistochemistry, western blot, flow cytometry sorting and animal experiments et al, we will study whether the mutant HIF1α modified MSCs promote differentiation of MSCs into osteoblast and homing of EPCs to the ischemic site, and further explore the mechanism that mutant HIF1α modified MSCs enhance the angiogenetic effects of EPCs by exosomes. It may provide a new way for the treatment of femoral head necrosis.