Transplantation of mesenchymal stem cells in a canine disc degeneration model

Transplantation of mesenchymal stem cells in a canine disc degeneration model
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DOI:
10.1002/jor.20584
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发表时间:
2008-05-01
影响因子:
2.8
通讯作者:
Sakai, Daisuke
Sakai, Daisuke
中科院分区:
医学3区
文献类型:
--
作者:
Hiyama, Akihiko;Mochida, Joji;Sakai, Daisuke

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间充质干细胞(MSCs)移植可有效减缓小动物椎间盘退变这种新疗法在大型动物或人类身上的应用还有很多未知之处。fas -配体(FasL)仅存在于具有孤立免疫特权的组织中,在ivd中表达,特别是在髓核(NP)中。维持FasL水平对IVD功能很重要。本研究在犬椎间盘退变模型中评估MSC移植是否对椎间盘退变的抑制和免疫特权的保存有影响。成年比格犬分为正常对照组(NC)、MSC组和椎间盘退变(仅核切除)组。骨髓间充质干细胞组,核切除后4周,将骨髓间充质干细胞移植到退变诱导的椎间盘中。术后随访12周。随后进行放射学、组织学、生化、免疫组织化学和RT-PCR分析。间充质干细胞移植可有效促进退变椎间盘的再生。移植前MSCs的FACS和RT-PCR分析表明,MSCs在遗传水平上表达FasL,而不是在蛋白质水平上表达FasL。移植后8周在NP区检测到gfp阳性的MSCs表达FasL蛋白。本研究结果表明,MSC移植可能通过将移植的MSCs分化为表达FasL的细胞而有助于维持IVD免疫特权。0 2008骨科研究学会。
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. 0 2008 Orthopaedic Research Society.