摘要
目的探讨转化生长因子-β1（TGF-β1）基因转染间充质干细胞（MSCs）能否提高关节软骨缺损的修复质量。方法将TGF-β1基因转入关节软骨种子细胞MSCs中，并与涂覆多聚赖氨酸的复合外消旋聚乳酸（PDLLA）可降解多孔仿生基质材料复合移植，修复同种异体兔关节软骨缺损。以单纯空载体转染MSCs为对照，通过组织学、电镜及免疫组织化学等方法检测。结果（1）转基因细胞-仿生基质材料体外复合培养扫描电镜观察证实TGF-β1基因修饰的MSCs的增殖分化活性明显优于对照组，差异有统计学意义（x^2=5．203，P=0．013）。（2）体内实验组织学及透射电镜结果显示实验组新生组织为透明样软骨，关节面平整，软骨下骨完全再生，与宿主骨软骨结合紧密，未见免疫排斥反应，对照组则新生软骨质量欠佳，与宿主骨整合欠佳，有不同程度的免疫排斥反应。（3）免疫组织化学结果显示转基因细胞可继续表达TGF-β1，至少4周以上。（4）术后第24周实验组的最大负荷、抗弯强度及载荷／位移比对照组分别提高了65．12％、40．78％及35．29％，差异有统计学意义（t=7．418、5．131、2．838，P=0．001、0．003、0．036）。而实验组弹性模量与对照组比较提高了13．59％，差异无统计学意义（t=1．455，P=0．112）。结论TGF-β1基因修饰的MSCs-仿生基质材料能有效提高关节软骨缺损，特别是创伤和骨关节炎关节软骨缺损的修复质量。
Objective To investigate whether the mesenchymal stem cells （MSCs） transfected with transforming growth factor -β1 （ TGF -β1 ） gene can improve the quality and long - term efficacy of articular cartilage defect repair. Methods MSCs were transfected with TGF-β1 gene, and transplanted in combination with poly lysine coated with poly lactic acid biodegradable DL porous biomimetic matrix materials in repairing articular cartilage defect （experimental group）. MSCs transfected with simple empty vector served as controls. Histological examinations, electron microscopy and immunohistochemistry were used. Results The results showed that the TGF-β1, the MSCs and the proliferation and differentiation activity of the modified ceils were significantly better than those of the control group in vitro （x^2 = 5. 203, P = 0. 013 ）. In vivo histology and transmission electron microscopy results showed that the new experimen- tal group for transparent cartilage, subchondral bone and joint formation, complete regeneration, closely integrated with the host bone cartilage, no immune rejection, the control group of new cartilage of poor quali- ty, poor integration with host bone, there are varying degrees of immune rejection. Immunohistochemistry results showed that transgenic cells can continue to express TGF -β1, at least 4 weeks. Experimental group after twenty - fourth weeks the maximum load, flexural strength and load/displacement than in the control group were increased by 65.12% , 40. 78% and 35.29% , the difference was statistically significant （t =7. 418, 5. 131 and 2. 838, P =0. 001, 0. 003 and 0. 036）. The elastic modulus of the experimental group and the control group increased by 13.59%, the difference was not statistically significant （ t = 1. 455, P = 0. 112）. Conclusion TGF-β1 gene modified MSCs/biomimetic matrix materials can effectively improve the quality of articular cartilage defects, especially in the repair of articular cartilage defects.
出处
《中华实验外科杂志》
CSCD
北大核心
2017年第6期942-945,共4页
Chinese Journal of Experimental Surgery
关键词
关节软骨缺损修复
间充质干细胞
转化生长因子-Β1
基因转染
Articular cartilage defect repair
Mesenchymal stem ceils
Transforming growth factor -β1
Gene transfection
