关节软骨缺损工程组织修复后退变机理和防止方法的研究

The cell based technique to articular cartilage repairing, such as the injection of chondrocytes under the periosteum and the transplantation of tissue engineered cartilage, was showing its promising future, but the degeneration of repaired tissue was a common phenomenon. There were several kinds of "seed cell", which include adult chondrocytes, mesenchymal stem cell of bone merrow, epiphyseal chondrocytes, embryonic chondrocytes and adHGF gene transferred mesenchymal stem cell were cultured and the tissue engineered cartilage were constructed in combine with monolayer or bilayer biodegradable PLGA scaffold in vitro, then the engineered cartilage was used to repaired the cartilage defects. so as to the repairing capability of each "seed cell"was compared, the effects of the cytokines to "seed cell" in metabolism, prolifilation and phenotype were researched as well. Besides, the possibility of using gene transferred mesenchymal stem cell in articular cartilage repairing was studied. The results of this study suggest that the adult chondrocyte can be induced to be secondary chondroprogenitors with TGF-β1 and bFGF, which can be used to construct tissue engineered cartilage. The treatment of adult articular cartilage defects with autogenous tissue engineered construct may lead to good results. The mesenchymal stem cell could expressed chondrocytic phenotype under certain condition, and the mesenchymal stem cell could be used to be the carriers of the transgenes. The mesenchymal stem cell transduced with the adHGF gene could express the characteristic Colα1(II) of chondrocytes. Besides, the apoptotic cells were observed in the interspace of repair tissue and cargilage, which probably impair the articular cartilage repairing effects. The results suggested the activity of the prolifilation and the final differentiation of the "seed cell" could lead to the degeneration of the repair tissue, so the repairing results were impaired. The results also suggested the bilayer biodegradable PLGA scaffold has better results in cartilage repairing. The study about the retro- differentiation of the adult chondrocytes and the construction of autogenous tissue engineered cartilage had realistic meaning in the articular cartilage repairing of adult or aged patients, the study also complement the knowledge of metabolism, prolifilation and phenotype of the adult chondrocytes.

拟建立用于组织工程多种软骨种子细胞的培养的方法，并研究组织工程软骨不同来源种子细胞的分化、凋亡、免疫和细胞迁移与修复组织退变的关系，探讨工程软骨修复关节软骨缺损后退变的有关机理，从而筛选也最佳的种子细胞。同时通过研究细胞因子对细胞上述方面的调节，设计新型细胞因子缓释载体，达到抑制软骨移植交界区的免疫反应和细胞凋亡，并促进软骨迁移。最终达到防止退变的目的。