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间质干细胞通过软骨细胞分化和刺激内源性细胞来阻止椎间盘退变。

Mesenchymal stem cells arrest intervertebral disc degeneration through chondrocytic differentiation and stimulation of endogenous cells.

机构信息

Department of Orthopaedics and Traumatology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, People's Republic of China.

出版信息

Mol Ther. 2009 Nov;17(11):1959-66. doi: 10.1038/mt.2009.146. Epub 2009 Jul 7.

Abstract

Degenerative disc disease (DDD) is a common disease which affects millions of people. Autograft of the bone marrow derived mesenchymal stem cells (BMSCs) have been shown to have the ability to arrest degeneration in rabbit and canine intervertebral discs. In this study, we have used the mouse model to investigate the mechanism of degeneration arrest. BMSC from Egfp transgenic mice were injected into the degenerated murine intervertebral discs induced by annular puncture. We found that BMSC could arrest the progressive degeneration of the discs with significant regeneration of the nucleus pulposus (NP). In the regeneration, expression of proteoglycan genes were upregulated and extracellular matrix (ECM) progressively accumulated in the NP after BMSC injection. Combined in situ hybridization and immunohistochemistry revealed that BMSC underwent chondrocytic differentiation in the regeneration process. Interestingly, BMSC-induced an increase of endogenous notochordal cells in NP and expression of chondrocytic markers. In this study, we have firstly shown that the BMSC could arrest the degeneration of the murine notochordal NP and contribute to the augmentation of the ECM in the NP by both autonomous differentiation and stimulatory action on endogenous cells.

摘要

退行性椎间盘疾病(DDD)是一种常见疾病,影响着数以百万计的人。自体骨髓间充质干细胞(BMSCs)移植已被证明具有阻止兔和犬椎间盘退变的能力。在这项研究中,我们使用小鼠模型来研究退变阻滞的机制。将来自 Egfp 转基因小鼠的 BMSC 注射到通过环状穿刺诱导的退变的鼠椎间盘内。我们发现 BMSC 可以阻止椎间盘的进行性退变,显著促进髓核(NP)的再生。在再生过程中,BMSC 注射后蛋白聚糖基因的表达上调,细胞外基质(ECM)逐渐在 NP 中积累。原位杂交和免疫组织化学结合显示,BMSC 在再生过程中经历了软骨细胞分化。有趣的是,BMSC 诱导 NP 中内源性脊索细胞的增加和软骨细胞标志物的表达。在这项研究中,我们首次表明 BMSC 可以阻止鼠脊索 NP 的退变,并通过自主分化和对内源性细胞的刺激作用,有助于 NP 中 ECM 的增加。

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