免疫逃逸及生物力学方法构建关节组织工程软骨

Immune escape and biomechanics in the construction of tissue engineered cartilage tissue

背景:机械应力在软骨组织工程中起着十分重要的作用,但应力对异体种子细胞诱导分化的作用研究较少,应力促进异体干细胞向软骨细胞分化的机制尚不清楚。目的:探讨降低干细胞的免疫原性以最终将异体种子细胞构建的组织工程化软骨应用于临床的可能性。方法:应用计算机检索2000年1月至2012年1月PubMed数据库相关文章,检索词为"engineered articular cartilage tissue,cartilage immune,articular cartilage,biomechanical"。共检索到文献510篇,最终纳入符合标准的文献33篇。结果与结论:利用干细胞多向分化潜能将其诱导分化为成软骨细胞,研究力学载荷对软骨细胞的影响、力学信号的传导机制以便应用生物反应器将软骨细胞进行大规模扩增;利用基因打靶技术可使体外培养的干细胞染色体DNA与外源性同源序列发生重组,达到定点修饰改造细胞β2-微球蛋白基因的目的,降低干细胞主要组织相容性复合体Ⅰ类分子的表达,从而降低其免疫原性,为软骨组织工程提供低免疫原性的种子细胞。

BACKGROUND：Mechanical stress plays a very important role in cartilage tissue engineering,but there are fewer studies on stress induced allogeneic seed cell differentiation and the mechanism of stress to promote differentiation of allogeneic stem cells into chondrocytes is still unclear.OBJECTIVE：To explore the feasibility of reducing immunogenicity of stem cells to apply allogeneic seed cells in the construction of tissue-engineered cartilage in clinic.METHODS：A computer-based search of PubMed（2000-01/2012-01） was performed using the key words of ＂engineered articular cartilage tissue,cartilage immune,articular cartilage,biomechanical＂.The language was limited to English.Totally 510 articles were retrieved,and finally 33 articles were included in result analysis.RESULTS AND CONCLUSION：Stem cells with multilineage differentiation potential differentiate into chondrocytes.Mechanical load effects on chondrocytes and mechanical signal transduction mechanism have been explored to carry out a large-scale proliferation of chondrocytes using bioreactor.Gene targeting technology enables the recombination of chromosomal DNA from stem cells cultured in vitro and exogenous homologous sequence to modify β2-microglobulin gene,reduce the immunogenicity of stem cells,and provide low-immunogenicity seed cells for cartilage tissue engineering.