Osteogenic and chondrogenic differentiation of embryonic stem cells in response to specific growth factors
Osteogenic and chondrogenic differentiation of embryonic stem cells in response to specific growth factors
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DOI：
10.1016/j.bone.2004.07.019
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发表时间：
2005-05-01
期刊：
影响因子：
4.1
通讯作者：
Smith, AG
中科院分区：
文献类型：
--
作者：
Kawaguchi, J;Mee, PJ;Smith, AG
多能胚胎干细胞（ES）在体外可靠地转化为骨和软骨形成细胞将扩大骨骼发生实验研究的机会，并且还可以为药物筛选和细胞治疗应用提供新的细胞来源。在这里，我们评估了用视黄酸处理胚状体后小鼠 ES 细胞间充质细胞谱系的产生，此前有报道称视黄酸可诱导脂肪细胞前体的发育。我们发现视黄酸减少中胚层分化，但增强神经嵴标记物的表达，神经嵴标记物是间充质成分的替代来源。 Runx1 和 Ptprv 似乎提供了间充质潜能的早期标记。随后，不同的间充质命运因特定的生长因子而产生。用骨形态发生蛋白 (BMP-4) 替代脂肪形成因子胰岛素和三碘甲状腺原氨酸，可抑制脂肪形成和成熟成骨表型的发育。相反，用转化生长因子-β (TGF-(β(3)) 治疗可促进软骨分化。因此，使用适当的生长因子和培养环境可引导 ES 细胞衍生的前体细胞分化为不同的间充质区室。(c) 2005 Elsevier Inc. 保留所有权利。
Reliable in vitro conversion of pluripotent embryonic stein (ES) cells into bone and cartilage-forming cells would expand opportunities for experimental investigations of skeletogenesis and could also provide new cellular sources for pharmaceutical screening and for cell therapy applications. Here, we evaluate the generation of mesenchymal cell lineages from mouse ES cells following treatment of embryoid bodies with retinoic acid, previously reported to induce development of adipocyte precursors. We find that retinoic acid reduces mesodermal differentiation but enhances expression of markers of neural crest, an alternative origin of mesenchymal elements. Runx1 and Ptprv appear to provide early markers of mesenchymal potential. Subsequently, different mesenchymal fates are generated in response to particular growth factors. Substitution of the adipogenic factors insulin and triiodothyronine with bone morphogenetic protein (BMP-4) results in suppression of adipogenesis and development of a mature osteogenic phenotype. In contrast, treatment with transforming growth factor-beta (TGF-(beta(3)) promotes chondrogenic differentiation. Thus, the use of appropriate growth factors and culture milieu steers differentiation of ES cell-derived precursors into distinct mesenchymal compartments. (c) 2005 Elsevier Inc. All rights reserved.