MSCs和ECs共移植体系联同AngⅡ对早期股骨头坏死的修复作用及机制研究

股骨头坏死（ONFH）是由于骨组织的血供障碍引起骨细胞进行性死亡的疾病，其发病机制尚不清楚，且无理想的治疗手段。骨髓间充质干细胞(BMSCs)移植是目前治疗早期ONFH的研究热点，但仍未有突破。本课题拟以BMSCs和内皮细胞（ECs）作为种子细胞为切入点，联合血管紧张素Ⅱ（Ang Ⅱ）以促进共移植细胞对早期ONFH的修复作用。通过细胞分子生物学相关技术探讨骨修复因子和血管新生因子的表达情况，并结合影像学和病理学手段评估其疗效，最终建立应用Ang Ⅱ诱导的BMSCs和ECs共移植体系治疗ONFH的新技术平台。迄今此治疗方案修复早期ONFH的机制尚不清楚，本项目将进一步在细胞分子水平探讨其治疗ONFH的信号通路。该项目有望初步阐明BMSCs和ECs共移植体系在Ang Ⅱ作用下修复早期ONFH的新的分子机制，为ONFH的治疗提供了一种新的思路，并为其最终应用于临床提供理论基础和实验依据。

Osteonecrosis of the femoral head is a progressive disease of bone necrosis, caused by the impairment or failure of blood supply in bone tissue. By far, the underlying mechanism of its pathology is still unclear, and there is no effective treatment for it. Although bone marrow mesenchymal stem cells (BMSCs) transplantation, as a research hotspot in the medical field, has widely been used for the treatment of early ONFH, it is still not achieved a substantial breakthrough. In this present study, BMSCs and endothelial cells (ECs) of transplantation into the necrotic area of the femoral head in combination with angiotensin Ⅱ(Ang Ⅱ) stimulation were used to treat early ONFH. Concomitantly, the expressions of bone regeneration factors, angiogenesis factors and transcription factors etc., were detected by using a series of cellular and molecular assays. The therapeutic efficacy is further evaluated by using imagology and pathological methods. On the basis of these results, we will develop a novel and efficient technical platform for treating ONFH by using Ang Ⅱ-induced BMSCs and ECs co-transplantation. Moreover, the molecular mechanism underlying this special treatment for early ONFH is not elusive. Therefore the project will further reveal the signaling pathway for treatment of ONFH at the cellular and molecular levels. In summary, the present study will elucidate the possible molecular mechanism of Ang Ⅱ-induced co-transplantation of BMSCs and ECs on repair of early stage ONFH, and may provide a new therapeutic model for ONFH and theoretical basis for clinical application.