Liu He, Ding Jianxun, Wang Jincheng, Wang Yinan, Yang Modi, Zhang Yanbo, Chang Fei, Chen Xuesi
Department of Orthopedics, The Second Hospital of Jilin University, Changchun, P. R. China.
Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, P. R. China.
PLoS One. 2015 Mar 16;10(3):e0120596. doi: 10.1371/journal.pone.0120596. eCollection 2015.
The persistent inflammation of rheumatoid arthritis (RA) always leads to partial synovial hyperplasia and the destruction of articular cartilage. Bone marrow mesenchymal stem cells (BMMSCs) have been proven to possess immunosuppressive effects, and widely explored in the treatment of autoimmune diseases. However, poor inhibitory effect on local inflammatory state and limited capacity of preventing destruction of articular cartilage by systemic BMMSCs transplantation were observed. Herein, toward the classical type II collagen-induced arthritis in rats, the combination treatment of microfracture and in situ transplantation of thermogel-encapsulated BMMSCs was verified to obviously down-regulate the ratio of CD4+ to CD8+ T lymphocytes in peripheral blood. In addition, it resulted in the decreased levels of inflammatory cytokines, such as interleukin-1β, tumor necrosis factor-α and anti-collagen type II antibody, in the serum. Simultaneously, the combination therapy also could inhibit the proliferation of antigen specific lymphocytes and local joint inflammatory condition, and prevent the articular cartilage damage. The results indicated that the treatment programs could effectively stimulate the endogenous and exogenous BMMSCs to exhibit the immunosuppression and cartilage protection capability. This study provided a new therapeutic strategy for autoimmune inflammatory diseases, such as RA.
类风湿性关节炎(RA)的持续炎症总是导致部分滑膜增生和关节软骨破坏。骨髓间充质干细胞(BMMSCs)已被证明具有免疫抑制作用,并在自身免疫性疾病的治疗中得到广泛探索。然而,观察到全身BMMSCs移植对局部炎症状态的抑制作用较差,且预防关节软骨破坏的能力有限。在此,针对大鼠经典的II型胶原诱导性关节炎,微骨折联合热凝胶包裹的BMMSCs原位移植的联合治疗被证实可明显下调外周血中CD4+与CD8+ T淋巴细胞的比例。此外,它还导致血清中炎症细胞因子如白细胞介素-1β、肿瘤坏死因子-α和抗II型胶原抗体水平降低。同时,联合治疗还可抑制抗原特异性淋巴细胞的增殖和局部关节炎症状态,并防止关节软骨损伤。结果表明,该治疗方案可有效刺激内源性和外源性BMMSCs发挥免疫抑制和软骨保护能力。本研究为RA等自身免疫性炎症疾病提供了一种新的治疗策略。