Morphogenetic signals from chondrocytes promote chondrogenic and osteogenic differentiation of mesenchymal stem cells
Morphogenetic signals from chondrocytes promote chondrogenic and osteogenic differentiation of mesenchymal stem cells
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DOI：
10.1002/jcp.21052
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发表时间：
2007-08-01
影响因子：
5.6
通讯作者：
Elisseeff, Jennifer
中科院分区：
文献类型：
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作者：
Hwang, Nathaniel S.;Varghese, Shyni;Elisseeff, Jennifer
间充质干细胞(MSCs)在肌肉骨骼组织工程中具有潜在的应用价值。然而，在体内控制MSC的分化和组织形成仍然是一个挑战。需要明确定义的有效协议来指导MSC在体内的行为。我们推测软骨细胞的形态发生信号可能调节MSC的分化。在MSCs的微团培养中，与软骨细胞条件培养液(CCM)孵育显著促进了包括11型胶原在内的软骨特异性基质的产生。此外，MSCs与添加成骨因子的条件培养液孵育后，可诱导更多的成骨和钙的积累，并增加碱性磷酸酶的活性。这些发现表明，软骨细胞分泌的因子在体外微团培养过程中促进了MSCs的软骨生成和成骨。此外，用软骨细胞条件培养液扩增的MSCs被包裹在水凝胶中，然后移植到裸鼠体内，新生骨细胞的嗜碱性细胞外基质沉积特征明显。这些结果表明，关节软骨细胞在体外和体内都能产生合适的形态发生因子，诱导MSCs的分化程序。
Mesenchymal stem cells (MSCs) are potentially useful cells for musculoskeletal tissue engineering. However, controlling MSC differentiation and tissue formation in vivo remains a challenge. There is a significant need for well-defined and efficient protocols for directing MSC behaviors in vivo. We hypothesize that morphogenetic signals from chondrocytes may regulate MSC differentiation. In micromass culture of MSCs, incubation with chondrocyte-conditioned medium (CCM) significantly enhanced the production of cartilage specific matrix including type 11 collagen. In addition, incubation of MSCs with conditioned medium supplemented with osteogenic factors induced more osteogenesis and accumulation of calcium and increased ALP activity. These findings reveal that chondrocyte-secreted factors promote chondrogenesis as well as osteogenesis of MSCs during in vitro micromass culture. Moreover, when MSCs expanded with chondrocyte-conditioned medium were encapsulated in hydrogels and subsequently implanted into athymic mice, basophilic extracellular matrix deposition characteristic of neocartilage was evident. These results indicate that articular chondrocytes produce suitable morphogenetic factors that induce the differentiation program of MSCs in vitro and in vivo.