Transplantation of mesenchymal stem cells in a canine disc degeneration model

间充质干细胞 豁免特权 移植 Fas配体 病理 变性(医学) 干细胞 免疫系统 医学 生物 免疫学 细胞凋亡 细胞生物学 外科 程序性细胞死亡 遗传学
作者
Akihiko Hiyama,Joji Mochida,Toru Iwashina,Hiroko Omi,Takuya Watanabe,Kenji Serigano,Futoshi Tamura,Daisuke Sakai
出处
期刊:Journal of Orthopaedic Research [Wiley]
卷期号:26 (5): 589-600 被引量:240
标识
DOI:10.1002/jor.20584
摘要

Abstract Transplantation of mesenchymal stem cells (MSCs) is effective in decelerating disc degeneration in small animals; much remains unknown about this new therapy in larger animals or humans. Fas‐ligand (FasL), which is only found in tissues with isolated immune privilege, is expressed in IVDs, particularly in the nucleus pulposus (NP). Maintaining the FasL level is important for IVD function. This study evaluated whether MSC transplantation has an effect on the suppression of disc degeneration and preservation of immune privilege in a canine model of disc degeneration. Mature beagles were separated into a normal control group (NC), a MSC group, and the disc degeneration (nucleotomy‐only) group. In the MSC group, 4 weeks after nucleotomy, MSCs were transplanted into the degeneration‐induced discs. The animals were followed for 12 weeks after the initial operation. Subsequently, radiological, histological, biochemical, immunohistochemical, and RT‐PCR analyses were performed. MSC transplantation effectively led to the regeneration of degenerated discs. FACS and RT‐PCR analyses of MSCs before transplantation demonstrated that the MSCs expressed FasL at the genetic level, not at the protein level. GFP‐positive MSCs detected in the NP region 8 weeks after transplantation expressed FasL protein. The results of this study suggest that MSC transplantation may contribute to the maintenance of IVD immune privilege by the differentiation of transplanted MSCs into cells expressing FasL. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:589–600, 2008
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