外周血干细胞生物学特性及其复合仿生支架修复关节软骨缺损的实验研究

项目名称： 外周血干细胞生物学特性及其复合仿生支架修复关节软骨缺损的实验研究

项目编号： No.51273004

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 一般工业技术

项目作者： 余家阔

作者单位： 北京大学

项目金额： 80万元

中文摘要： 受直接移植自体外周血MSCs（PB-MSCs）修复运动员软骨缺损成功并在兔膝关节得到验证启发，考虑到PB-MSCs具有获取损伤小、硬件要求低和临床合法性好的优势，本研究对外周血和骨髓源MSCs的生物学特性进行比较，试图证明PB-MSCs可做为新种子细胞用于软骨损伤修复。采用三维多孔脱钙松质骨和RGD多肽修饰聚氨基酸/多糖复合水凝胶支架制备不同的仿生软骨支架材料。通过研究细胞外基质（ECM）微环境、生物活性脱矿松质骨支架微环境和软骨损伤区微环境对不同组织工程软骨方案效果的影响，以及这些微环境是否足以促成植入的未诱导分化的MSCs对软骨损伤的修复全过程，同时研究不同支架对软骨修复效果的影响。辅以Y性染色体探针原位杂交和基因芯片检测基因差异性表达，研究新生的修复组织是否来自植入的MSCs。本研究有利于探索新种子细胞、仿生支架和微环境相结合的更佳的组织工程软骨方案的研究，更利于研究结果的临床转化。

中文关键词： 间充质干细胞；软骨缺损；组织工程；水凝胶；外周血

英文摘要： Ideas of this study derived from successful clinical knee trochlea cartilage repair with directly transplanted patient's autologous peripheral blood mesenchymal stem cells (PB-MSCs) covered with autologous periosteum. The PB-MSCs could be obtained with minimally hurt,not special instruments needed and it also has the advantage of legally clinical application.This research will do comparative study on the biological characteristics of the PB-MSCs and the bone marrow derived MSCs,try to demonstrate the PB-MSCs could be used as seeded cells for cartilage repair. 3D porous demineralized cancellous bone and RGD poly peptide modifyed polypeptide/polysaccharides composite scaffolds will be used to make different biomimetic scafflods. The microenvironments' influence of the ECM,the biologically active demineralized cancellous bone scaffold, and the cartilage injury site on the different tissue engineered cartilage schemes will be investigated. Try to find if these microenvironments could promote the whole process of injuryed cartilage repair by implanting undifferentiated MSCs. At the same time, effects of different scaffolds on the cartilage repair will also be studied. This study has the advantage of research on better tissue engineered cartilage schemes combining new seeded cells,biomimetic scaffolds and microenviro

英文关键词： Mesenchymal stem cells；Cartilage defect；tissue engineering；hydrogel；peripheral blood