Endogenous Collagen Influences Differentiation of Human Multipotent Mesenchymal Stromal Cells
Endogenous Collagen Influences Differentiation of Human Multipotent Mesenchymal Stromal Cells
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DOI：
10.1089/ten.tea.2009.0341
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发表时间：
2010-05-01
影响因子：
4.1
通讯作者：
de Boer, Jan
中科院分区：
文献类型：
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作者：
Fernandes, Hugo;Mentink, Anouk;de Boer, Jan
人多能间充质基质细胞（human multipotent mesenchymal stromal cells，hMSCs）是一种多能细胞，在适当的刺激下，可以分化成不同的谱系，如成骨、成软骨和成脂谱系。在抗坏血酸存在下，MSC分泌主要由I型胶原组成的细胞外基质。在这里，我们评估了内源性胶原合成在hMSC分化和干细胞维持中的潜在作用。我们观察到在没有抗坏血酸的情况下，hMSCs的增殖率急剧下降，同时体外成骨和体内骨形成减少。与I型胶原在成骨中的积极作用一致，在不存在抗坏血酸的情况下培养的hMSCs的基因表达谱显示参与脂肪形成和软骨形成的基因的表达增加，成骨基因的表达减少。我们还观察到，抗坏血酸存在下，基质重塑和抗破骨细胞生成信号高。在hMSCs的扩增阶段，I型胶原的存在并不影响其成骨和成脂分化潜能。总之，胶原基质支持成骨hMSCs的增殖和分化，但另一方面，呈现刺激基质重塑和抑制破骨细胞生成的信号。
Human multipotent mesenchymal stromal cells (hMSCs) are multipotent cells that, in the presence of appropriate stimuli, can differentiate into different lineages such as the osteogenic, chondrogenic, and adipogenic lineages. In the presence of ascorbic acid, MSCs secrete an extracellular matrix mainly composed of collagen type I. Here we assessed the potential role of endogenous collagen synthesis in hMSC differentiation and stem cell maintenance. We observed a sharp reduction in proliferation rate of hMSCs in the absence of ascorbic acid, concomitant with a reduction in osteogenesis in vitro and bone formation in vivo. In line with a positive role for collagen type I in osteogenesis, gene expression profiling of hMSCs cultured in the absence of ascorbic acid demonstrated increased expression of genes involved in adipogenesis and chondrogenesis and a reduction in expression of osteogenic genes. We also observed that matrix remodeling and anti-osteoclastogenic signals were high in the presence of ascorbic acid. The presence of collagen type I during the expansion phase of hMSCs did not affect their osteogenic and adipogenic differentiation potential. In conclusion, the collagenous matrix supports both proliferation and differentiation of osteogenic hMSCs but, on the other hand, presents signals stimulating matrix remodeling and inhibiting osteoclastogenesis.