肝细胞生长因子调节人骨髓基质干细胞成骨分化的效应与机制

股骨头缺血性坏死（ANFH）是临床多发病和常见病，致残率极高，目前尚无特效疗法。骨髓基质干细胞（BMSC）移植疗法治疗ANFH前景广阔。项目组前期在863计划的资助下，建立了肝细胞生长因子（HGF）基因修饰BMSC移植联合髓芯减压治疗早期ANFH的技术平台，其可行性和有效性在动物模型中获得验证；进一步探讨疗效产生的机制，发现HGF水平可调控BMSC的增殖与成骨分化。本项目拟在人BMSC中找到调控BMSC增殖与成骨分化的最适HGF基因修饰水平，并进一步探讨HGF及其受体c-Met下游信号通路在此过程中的调控机制，同时获得可辅助HGF诱导成骨的最佳信号通路特异性抑制剂/激活剂使用方案，进而在兔早期激素性ANFH模型中进行验证。本项目将为HGF基因修饰BMSC移植治疗早期ANFH的临床应用提供更坚实的依据。

Avascular necrosis (ANFH) is frequently occurring in clinic with high morbidity. Although there is no effective therapy for ANFH at present, bone marrow stromal stem cell (BMSC) transplantation holds great promise. Previously supported by State 863 Projects, we made the first attempt to develop the therapeutic technology platform for early ANFH based on transplantation of hepatocyte growth factor (HGF) gene-modified BMSC in combination with core decompression. The feasibility and effectiveness of this original strategy obtained verification in the animal model. Further exploration of the mechanisms led to the finding that the HGF level is involved in the regulation of proliferation and osteogenic differentiation of BMSC. Based on our previous studies, we intend to find out the optimal levels of HGF gene modification for regulating proliferation and osteogenic differentiation of human BMSC. Further, we will explore the regulatory mechanisms by the HGF/c-Met signaling pathway in this process, and access to the best regimen of the specific signal pathway inhibitor / activator usage for assisting the osteo-inductive effects of HGF. Such assistant regimen is to be validated in the rabbit model of early hormonal ANFH. This project will provide more solid basis for the clinical application of HGF gene-modified BMSC transplantation for treatment of early ANFH.