Neotendon formation induced by manipulation of the Smad8 signalling pathway in mesenchymal stem cells
Neotendon formation induced by manipulation of the Smad8 signalling pathway in mesenchymal stem cells
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DOI：
10.1172/jci22689
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发表时间：
2006-04-01
影响因子：
15.9
通讯作者：
Gazit, D
中科院分区：
文献类型：
--
作者：
Hoffmann, A;Pelled, G;Gazit, D
组织再生需要招募成体干细胞，并将其分化为成熟的定向细胞。在这项研究中，我们描述了一种基于特定信号分子Smad8的肌腱再生的新方法，Smad8介导了间充质干细胞(MSCs)向肌腱样细胞的分化。将具有生物活性的Smad8突变体导入共表达成骨基因骨形态发生蛋白2(BMP2)的MSC FINE中。该工程细胞在体外和体内均显示了肌腱细胞的形态特征和基因表达谱。此外，在移植到跟腱部分缺损处后，双量子滤波MRI显示，该工程细胞能够诱导肌腱再生。这些结果表明，我们认为Smad8在促进肌腱分化的同时抑制了BMP2诱导的MSCs的成骨途径，这是一种新的机制。这些发现可能对肌腱或韧带的治疗替代以及对BMP在其中发挥关键发育作用的其他组织的工程化具有相当重要的意义。
Tissue regeneration requires the recruitment of adult stem cells and their differentiation into mature committed cells. In this study we describe what we believe to be a novel approach for tendon regeneration based on a specific signalling molecule, Smad8, which mediates the differentiation of mesenchymal stem cells (MSCs) into tendon-like cells. A biologically active Smad8 variant was transfected into an MSC fine that coexpressed the osteogenic gene bone morphogenetic protein 2 (BMP2). The engineered cells demonstrated the morphological characteristics and gene expression profile of tendon cells both in vitro and in vivo. In addition, following implantation in an Achilles tendon partial defect, the engineered cells were capable of inducing tendon regeneration demonstrated by double quantum filtered MRI. The results indicate what we believe to be a novel mechanism in which Smad8 inhibits the osteogenic pathway in MSCs known to be induced by BMP2 while promoting tendon differentiation. These findings may have considerable importance for the therapeutic replacement of tendons or ligaments and for engineering other tissues in which BMP plays a pivotal developmental role.