Chondrogenic differentiation of human embryonic stem cell-derived cells in arginine-glycine-aspartate modified hydrogels
Chondrogenic differentiation of human embryonic stem cell-derived cells in arginine-glycine-aspartate modified hydrogels
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DOI：
10.1089/ten.2006.12.2695
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发表时间：
2006-09-01
影响因子：
--
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
人类胚胎干细胞(HESCs)具有自我更新和生成多种细胞类型的潜力，为组织工程和再生医学应用提供关键的构建块。在此，我们描述了人胚胎干细胞向间充质样细胞的高效来源和向软骨方向的分化。这些细胞表现出间充质干细胞(MSC)的表面标记，包括CD29、CD44、CD105和血小板衍生生长因子受体-a。在适当的生长条件下，hESC来源的细胞增殖，没有表型变化，并保持MSC表面标志。在颗粒培养和外源性细胞外蛋白聚乙二醇二丙烯酸酯(PEGDA)水凝胶或精氨酸-甘氨酸-天冬氨酸(RGD)修饰的聚乙二醇二丙烯酸酯(PEGDA)水凝胶中研究细胞的软骨形成能力。HESC来源的细胞在颗粒培养中表现出生长因子依赖性的基质产生，但不能产生具有软骨形态特征的组织。在含有外源透明质酸或I型胶原的PEGDA水凝胶中，没有观察到明显的细胞生长或基质产生。相反，当这些细胞被包裹在RGD修饰的聚乙二醇水凝胶中时，在培养的3周内观察到具有嗜碱性细胞外基质沉积的新生软骨，产生软骨特异性基因上调和细胞外基质产生。我们的结果表明，可以从分化的hESCs到类胚体培养出具有MSC群体特征的前体细胞，从而为软骨组织工程提供潜在的无限细胞来源。
Human embryonic stem cells (hESCs) have the potential to self-renew and generate multiple cell types, producing critical building blocks for tissue engineering and regenerative medicine applications. Here, we describe the efficient derivation and chondrogenic differentiation of mesenchymal-like cells from hESCs. These cells exhibit mesenchymal stem cell (MSC) surface markers, including CD29, CD44, CD105, and platelet-derived growth factor receptor-a. Under appropriate growth conditions, the hESC-derived cells proliferated without phenotypic changes and maintained MSC surface markers. The chondrogenic capacity of the cells was studied in pellet culture and after encapsulation in poly( ethylene glycol)-diacrylate (PEGDA) hydrogels with exogenous extracellular proteins or arginine-glycine-aspartate (RGD)-modified PEGDA hydrogels. The hESC-derived cells exhibited growth factor dependent matrix production in pellet culture but did not produce tissue characteristic of cartilage morphology. In PEGDA hydrogels containing exogenous hyaluronic acid or type I collagen, no significant cell growth or matrix production was observed. In contrast, when these cells were encapsulated in RGD-modified poly(ethylene glycol) hydrogels, neocartilage with basophilic extracellular matrix deposition was observed within 3 weeks of culture, producing cartilage-specific gene up-regulation and extracellular matrix production. Our results indicate that precursor cells characteristic of a MSC population can be cultured from differentiating hESCs through embryoid bodies, thus holding great promise for a potentially unlimited source of cells for cartilage tissue engineering.