关节腔内骨髓间充质干细胞移植对类风湿性关节炎软骨的保护和修复作用

发布时间：2018-06-08 21:12

本文选题：骨髓间充质干细胞 + 软骨保护　；参考：《吉林大学》2015年硕士论文

【摘要】：背景：类风湿性关节炎总是伴随着关节滑膜增生和不同程度的软骨破坏。近来，骨髓间充质干细胞（BMMSCs）吸引了越来越多的关注。除了软骨分化能力，，它还表现出免疫抑制的特性，并已应用在各种自身免疫疾病的治疗中。以往关于BMMSCs对类风湿性关节炎的研究主要通过静脉或腹腔注射来观察其对免疫系统的影响。而对关节的炎症反应的抑制和防止软骨的持续性破坏的结果不佳。目的：应用经典的II型胶原诱导的大鼠关节炎模型进行胫骨平台钻孔后，将温敏性水凝胶包裹的BMMSCs原位注射于关节腔内，来观察其对软骨的保护作用。此外，在卵清蛋白诱导的兔关节炎模型中制造膝关节骨软骨缺损，将纤维蛋白凝胶包裹的BMMSCs原位移植，并评估其对全层软骨缺损的修复效果。结果：II型胶原诱导的大鼠关节炎模型中，间充质干细胞移植可以下调外周血中CD4+和CD8+淋巴细胞的比例；并能使血清中的炎性细胞因子，如白细胞介素-1和肿瘤坏死因子α，和II型胶原抗体的表达；此外，细胞移植还能抑制抗原特异淋巴细胞的增殖和关节局部的炎性反应、阻止关节软骨的进一步破坏。以上结果表明干细胞的局部移植联合微骨折术可以有效地发挥其免疫抑制能力，保护软骨的完整性。此外，在卵清蛋白诱导的兔类风湿性关节炎模型中，纤维蛋白凝胶包载的间充质干细胞在骨和软骨下骨缺损处可以发挥软骨修复的作用，并能改善关节局部的炎性环境，延缓软骨的进一步破坏。结论：间充质干细胞的局部移植联合微骨折术可以改善类风湿性关节炎的症状，诱导内源性干细胞发挥免疫抑制能力，保护软骨免于进一步的破坏，在骨和软骨下骨缺损处可以起到修复软骨缺损的作用。
[Abstract]:Background: rheumatoid arthritis is always associated with joint synovial hyperplasia and varying degrees of cartilage destruction. Recently, bone marrow mesenchymal stem cells (BMMSCs) attract more and more attention. In addition to cartilage differentiation, it has shown the characteristics of immunosuppression and has been used in the treatment of various autoimmune diseases. Previous BMMSCs pairs were used. The study of rheumatoid arthritis is mainly by intravenous or intraperitoneal injection to observe its effects on the immune system. The inhibition of the inflammatory response to the joints and the prevention of persistent destruction of the cartilage are poor.
Objective: to apply the classic II collagen induced rat arthritis model to the tibial plateau drilling, the thermosensitive hydrogel enwrapped BMMSCs was injected into the articular cavity to observe its protective effect on the cartilage. In addition, the osteochondral defect of the knee joint was made in the rabbit arthritis model induced by ovalbumin, and the fibrin gel was used. BMMSCs in situ was transplanted and the effect of repairing the full-thickness cartilage defect was evaluated.
Results: in the rat model of type II collagen induced arthritis, mesenchymal stem cell transplantation can reduce the proportion of CD4+ and CD8+ lymphocytes in peripheral blood, and the expression of inflammatory cytokines in the serum, such as interleukin -1 and tumor necrosis factor alpha, and II type collagen antibody. Moreover, cell transplantation can inhibit antigen specific drench. The proliferation of the cell and the local inflammatory reaction of the joint prevent the further destruction of the articular cartilage. The results show that the local transplantation of the stem cells combined with the micro fracture can effectively exert its immunosuppressive ability and protect the integrity of the cartilage. In addition, in the rabbit model of rheumatoid arthritis induced by ovalbumin, fibrin gel The entrapment of mesenchymal stem cells can play the role of cartilage repair at the bone and subchondral bone defects, and can improve the local inflammatory environment and delay the further damage of cartilage.
Conclusion: local transplantation of mesenchymal stem cells combined with micro fracture can improve the symptoms of rheumatoid arthritis, induce endogenous stem cells to play immunosuppressive ability, protect cartilage from further destruction, and play a role in repairing cartilage defects at the bone and subchondral bone defects.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R593.22

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