Chondrogenic differentiation of cultured human mesenchymal stem cells from marrow

Chondrogenic differentiation of cultured human mesenchymal stem cells from marrow
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DOI:
10.1089/ten.1998.4.415
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发表时间:
1998-12-01
期刊:
影响因子:
--
通讯作者:
Pittenger, MF
Pittenger, MF
中科院分区:
生物2区
文献类型:
--
作者:
Mackay, AM;Beck, SC;Pittenger, MF

文献摘要

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在成年人中,骨髓中的间充质干细胞(MSC)保留了沿着多种结缔组织谱系(包括软骨)增殖和分化的能力。在这项研究中,培养扩增的人骨髓间充质干细胞(hMSCs)的60人供体诱导表达软骨细胞的形态和基因产物。在含有100 nM地塞米松和10 ng/ml转化生长因子-β(3)(TGF-β(3))的成分确定的培养基中,通过在微团团块中培养hMSC诱导软骨形成。在14天内,细胞分泌的细胞外基质纳入II型胶原蛋白,聚集蛋白聚糖,和阴离子蛋白聚糖。通过添加50 nM甲状腺素、去除TGF-β(3)和将地塞米松浓度降低至1 nM,hMSCs可进一步分化为肥大状态。对软骨形成分化诱导的理解的增加应导致在确定负责软骨组织的产生、维持和再生的机制方面的进一步进展。
In the adult human, mesenchymal stem cells (MSCs) resident in bone marrow retain the capacity to proliferate and differentiate along multiple connective tissue lineages, including cartilage. In this study, culture-expanded human MSCs (hMSCs) of 60 human donors were induced to express the morphology and gene products of chondrocytes. Chondrogenesis was induced by culturing hMSCs in micromass pellets in the presence of a defined medium that included 100 nM dexamethasone and 10 ng/ml transforming growth factor-beta(3) (TGF-beta(3)). Within 14 days, cells secreted an extracellular matrix incorporating type II collagen, aggrecan, and anionic proteoglycans. hMSCs could be further differentiated to the hypertrophic state by the addition of 50 nM thyroxine, the withdrawal of TGF-beta(3), and the reduction of dexamethasone concentration to 1 nM. Increased understanding of the induction of chondrogenic differentiation should lead to further progress in defining the mechanisms responsible for the generation of cartilaginous tissues, their maintenance, and their regeneration.