掺锂异种脱蛋白骨复合SPIO和CM-Dil双标记的骨髓间充干细胞修复大段骨缺损的研究

项目名称： 掺锂异种脱蛋白骨复合SPIO和CM-Dil双标记的骨髓间充干细胞修复大段骨缺损的研究

项目编号： No.81472061

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 刘雷

作者单位： 四川大学

项目金额： 72万元

中文摘要： 各种原因引起的大段骨缺损是骨科临床上经常遇到的棘手问题之一，而寻找合 适的骨修复材料一直是骨科和生物材料领域面临的艰巨挑战。Wnt信号通路是调控MSCs向成骨细胞分化、增殖的关键通路。锂盐可以促进成骨，抑制糖原合成激酶3β(GSK-3β)阻断其对Wnt通路关键因子β-catenin磷酸化被认为是锂盐激活Wnt信号通路、促进成骨的基础。基于干细胞生物特性和生物材料协同的组织工程，具有生物活性的生物材料激活相关信号通路，调控MSCs定向成骨分化，促进组织、器官再生。本研究通过将锂盐复合入异种骨，同时符合SPIO、CM-Dil双标记MSCs，植入大段骨缺损的动物模型体内，利用分子影像技术追踪生物材料植入后MSCs的生物学行为，锂盐通过激活Wnt通路促进MSCs向成骨细胞分化、成骨，修复骨缺损、重建力学性能，获得良好的生物学和生物力学效果，为临床治疗大段骨缺损提供新思路和方法。

中文关键词： 骨组织工程；骨缺损；骨髓间充质干细胞；组织工程骨；组织工程

英文摘要： Large bone defects of various causes is one of the thorny problems frequently encountered in daily clinical pratice. Finding a proper bone repair material is still a chanllenge in the fileds of orthopedics and the biomaterial. Wnt signaling plays a vital role in the regulation proliferation and differentiation, and activites osteogenesis in MSCs under certain cellular contexts.Lithium is a mood stabilizing drug that affects embryonic development by altering cell fate and determination and pattern foramtion. Lithium inhibition of glycogen synthease kinase 3(GSK3) mimics the effects of canconical Wnt signaling. Activation of Wnt signaling leads to inhibition of GSK3 mediated phosphoxylation of a downstream transcription factor ?-catenin and prevents its sunsequent degradation by the preoteasome complex. Accumulation cytosolic ?-catenin then localizes to the nucleus and promotes the expression of genes regulated by Lef-Tcf transcription factor.The synergism of stem cell biologiy and biomaterial technology promises to have a profound impact on stem cell-base clinical application for tissue regeneration. In this study, we combined the lithium into the xenograft bone, cosistent with SPIO and CM-Dil double labelded MSCs, implanted in the animal models of the large bone defects. Also the molecular imaging technology is used to track the biological behavior of MSCs after the implantation of the biological material. Lithium salt can promote the MSCs to the osteoblast by activating the Wnt signaling pathway as to formate of the bone, repaire the bone defects and reublid the machnical properities. By doing so, can provide new ideas and methods to the clinical treatment of large bone defects.

英文关键词： Bone Tissue Engineering;Bone defect;MSCs;Tissue Engineering Bone;Tissue Engineering