Regenerative effects of transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated intervertebral disc
Regenerative effects of transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated intervertebral disc
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DOI：
10.1016/j.biomaterials.2005.06.038
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发表时间：
2006-01-01
期刊：
影响因子：
14
通讯作者：
Hotta, T
中科院分区：
文献类型：
--
作者：
Sakai, D;Mochida, J;Hotta, T
椎间盘退变（IVD）是人类腰痛的常见原因之一，是一种持续发展的现象，目前尚无有效的治疗方法。为了解决这一难题，我们将来自骨髓的自体间充质干细胞（MSCs）移植到兔椎间盘退变模型中，以确定干细胞是否可以修复退变的ivd。在诱导变性2周后，将表达LacZ的MSCs移植到兔L2-L3、L3-L4和L4-L5 ivd中。在24周的时间里，对未手术的正常对照（NC）、仅诱导椎间盘退变的假手术对照（NC）和msc移植动物的椎间盘高度、磁共振成像（MRI） t2加权信号强度、组织学、免疫组织化学和基质相关基因表达的变化进行评估。结果显示，msc移植后24周，与NC组相比，msc移植组动物退变椎间盘恢复了约91%的椎间盘高度值，MRI信号强度约81%。假手术组椎间盘高度值约67%，MRI信号强度约60%。宏观和组织学评价证实，与假手术椎间盘结构模糊相比，骨髓间质干细胞移植椎间盘的细胞核相对保存，呈环状结构。免疫组织化学和基因表达分析表明，移植的间充质干细胞椎间盘恢复了蛋白多糖的积累。这些数据表明，MSCs移植有效地导致兔椎间盘退变模型的ivd再生，正如我们之前的初步研究所表明的那样。间充质干细胞可作为细胞移植治疗退行性椎间盘疾病的宝贵资源。(c) 2005 Elsevier Ltd版权所有。
Intervertebral disc (IVD) degeneration, a common cause of low back pain in humans, is a relentlessly progressive phenomenon with no currently available effective treatment. In an attempt to solve this dilemma, we transplanted autologous mesenchymal stem cells (MSCs) from bone marrow into a rabbit model of disc degeneration to determine if stem cells could repair degenerated IVDs. LacZ expressing MSCs were transplanted to rabbit L2-L3, L3-L4 and L4-L5 IVDs 2 weeks after induction of degeneration. Changes in disc height by plain radiograph, T2-weighted signal intensity in magnetic resonance imaging (MRI), histology, immunohistochemistry and matrix associated gene expressions were evaluated between normal controls (NC) without operations, sham operated with only disc degeneration being induced, and MSC-transplanted animals for a 24-week period.Results showed that after 24 weeks post-MSC transplantation, degenerated discs of MSC-transplanted group animals regained a disc height value of about 91%, MRI signal intensity of about 81%, compared to NC group discs. On the other hand, shamoperated group discs demonstrated the disc height value of about 67% and MRI signal intensity of about 60%. Macroscopic and histological evaluations confirmed relatively preserved nucleus with circular annulus structure in MSC-transplanted discs compared to indistinct structure seen in sham. Restoration of proteoglycan accumulation in MSC-transplanted discs was suggested from immunohistochemistry and gene expression analysis. These data indicate that transplantation of MSCs effectively led to regeneration of IVDs in a rabbit model of disc degeneration as suggested in our previous pilot study. MSCs may serve as a valuable resource in cell transplantation therapy for degenerative disc disease. (c) 2005 Elsevier Ltd. All rights reserved.