David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 45 Carleton Street, E25-342, Cambridge, Massachusetts 02139, USA.
Biomacromolecules. 2010 Aug 9;11(8):1909-14. doi: 10.1021/bm100357t.
Embryonic stem cells (ESCs) are promising cell sources for tissue engineering and regenerative medicine. Scaffolds for ESC-based tissue regeneration should provide not only structural support, but also signals capable of supporting appropriate cell differentiation and tissue development. Extracellular matrix (ECM) is a key component of the stem cell niche in vivo and can influence stem cell fate via mediating cell attachment and migration, presenting chemical and physical cues, as well as binding soluble factors. Here we investigated the effects of combinatorial extracellular matrix proteins on controlled human ESC (hESC) differentiation. Varying ECM compositions in 3D markedly affects cell behavior, and optimal compositions of ECM hydrogels are identified that facilitate specific-lineage differentiation of stem cells. To our knowledge, this is the first combinatorial analysis of ECM hydrogels for their effects on hESC differentiation in 3D. The 3D matrices described herein may provide a useful platform for studying the interactive ECM signaling in influencing stem cell differentiation.
胚胎干细胞（ESCs）是组织工程和再生医学有前途的细胞来源。基于 ESC 的组织再生的支架不仅应提供结构支撑，还应提供能够支持适当的细胞分化和组织发育的信号。细胞外基质（ECM）是体内干细胞生态位的关键组成部分，可通过介导细胞附着和迁移、呈现化学和物理线索以及结合可溶性因子来影响干细胞命运。在这里，我们研究了组合细胞外基质蛋白对受控人 ESC（hESC）分化的影响。3D 中细胞外基质组成的变化显著影响细胞行为，确定了有利于干细胞特定谱系分化的细胞外基质水凝胶的最佳组成。据我们所知，这是首次对细胞外基质水凝胶在 3D 中对 hESC 分化的影响进行组合分析。本文所述的 3D 基质可为研究影响干细胞分化的细胞外基质信号交互作用提供有用的平台。
