功能性微血管化自体生物骨动态追踪及基因筛选

项目名称： 功能性微血管化自体生物骨动态追踪及基因筛选

项目编号： No.81460298

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 刘流

作者单位： 昆明医科大学

项目金额： 49万元

中文摘要： 骨移植术后因排异反应、血供不良，导致移植骨坏死、吸收，使骨缺损修复失败，且坏死物能对机体造成严重损伤。研发组织相容性好、血液供应充足及受机体调控的组织工程骨，是进入临床应用的关键。课题组前期研究表明，血管内皮细胞与骨髓间充质干细胞联合培养体系在细胞增殖、成骨方面均有明显优势；联合培养体系中存在BMP-2/Runx2 通路，但BMP-2 非Runx2 通路的唯一影响因子。本研究采用来源于自体具有优异新生血管能力的外周血内皮祖细胞（EPCs）及可分泌促管腔形成细胞因子的骨髓间充质干细胞（BMSCs）构建联合培养体系，复合脱蛋白生物骨（PDPBB）构建组织工程骨；基因芯片检测联合培养体系基因表达变化，筛选下游通路；对体外微血管管腔形成、成骨能力、活体内微循环血液灌流、骨缺损修复及排异情况等生物骨性能进行动态追踪。为构建无排异反应、微循环良好的自体组织工程生物骨应用于临床提供系统化技术支持。

中文关键词： 生物骨；微血管化；动态追踪；基因筛选；骨缺损

英文摘要： Necrosis and absorption of bone grafts caused by rejection and insufficient blood supply after bone transplantation, which induced failure of bone defect reconstruction and serious organism damage caused by sphacelus. The key point for clinic treatment of bone defect was to research and develop an engineering bone with good histocompatibility, microcirculation, no rejection and can be regulated by organism. The prophase research of our research group indicated that the cell proliferation and osteogenesis of vascular endothelial cells (VECs) and bone marrow stem cells (BMSCs) co-culture system were significantly better than single BMSCs, and there is BMP-2/Runx2 pathway in co-culture system, but BMP-2 was not the only affectoi of upstream pathway of Runx2. In this research, autologous EPCs with brilliant neovascularization capability isolated from peripheral blood and BMSCs with secretion capability of cytokine which can promoting lumen of blood vessel formation isolated from autologous bone marrow were co-cultured together, and seeded onto partially deproteinised biologic bone. The gene expression of co-culture system were screened with genechip, and downstream pathway of co-culture system are investigated. In vitro and vivo, the properties of engineering biological bone such as cell proliferation, immigration， lumen formation, the vascularization of EPCs，the osteogenesis of BMSCs, the osteogenesis, microcirculation formation, bone repair and rejection of engineering bone were dynamic monitored. The object of this research is to provide the systematized technology for constructing an autologous engineering biological bone with good histocompatibility， microvascularization and microcirculation, which can be fit for clinic application.

英文关键词： Biological bone;Microvascularization;Dynamic Tracking;Genescreen;Bone defect