Zhang Xiangmei, Yamaoka Kunihiro, Sonomoto Koshiro, Kaneko Hiroaki, Satake Makoto, Yamamoto Yuka, Kondo Masahiro, Zhao Jidong, Miyagawa Ippei, Yamagata Kaoru, Fukuyo Shunsuke, Okada Yosuke, Tanaka Yoshiya
The First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan.
Integrative Technology Research Institute, Teijin Limited, Tokyo, Japan.
PLoS One. 2014 Dec 4;9(12):e114621. doi: 10.1371/journal.pone.0114621. eCollection 2014.
Mesenchymal stem cells (MSC) have been used recently for the treatment of autoimmune diseases in murine animal models due to the immunoregulatory capacity. Current utilization of MSC requires cells in certain quantity with multiple courses of administration, leading to limitation in clinical usage. Here we efficiently treated collagen-induced arthritis rats with a single local implantation with reduced number of MSC (2∼20% of previous studies) with nano-fiber poly-lactic-co-glycolic acid (nano-fiber) scaffold. MSC seeded on nano-fiber scaffold suppressed arthritis and bone destruction due to inhibition of systemic inflammatory reaction and immune response by suppressing T cell proliferation and reducing anti- type II collagen antibody production. In vivo tracing of MSC demonstrated that these cells remained within the scaffold without migrating to other organs. Meanwhile, in vitro culture of MSC with nano-fiber scaffold significantly increased TGF-β1 production. These results indicate an efficient utilization of MSC with the scaffold for destructive joints in rheumatoid arthritis by a single and local inoculation. Thus, our data may serve as a new strategy for MSC-based therapy in inflammatory diseases and an alternative delivery method for bone destruction treatment.
由于间充质干细胞（MSC）具有免疫调节能力，最近已被用于治疗小鼠动物模型中的自身免疫性疾病。目前MSC的应用需要一定数量的细胞并进行多次给药，这导致了其临床应用的局限性。在此，我们使用纳米纤维聚乳酸-乙醇酸共聚物（纳米纤维）支架，通过单次局部植入数量减少的MSC（为先前研究的2%至20%），有效地治疗了胶原诱导性关节炎大鼠。接种在纳米纤维支架上的MSC抑制了关节炎和骨破坏，这是通过抑制全身炎症反应和免疫反应，抑制T细胞增殖并减少抗II型胶原抗体的产生实现的。对MSC的体内追踪表明，这些细胞保留在支架内，没有迁移到其他器官。同时，用纳米纤维支架对MSC进行体外培养可显著增加转化生长因子-β1的产生。这些结果表明，通过单次局部接种，可有效地利用带有支架的MSC治疗类风湿性关节炎中的破坏性关节。因此，我们的数据可能成为基于MSC治疗炎症性疾病的新策略，以及治疗骨破坏的替代递送方法。
