Tightly anchored tissue-mimetic matrices as instructive stem cell microenvironments
Tightly anchored tissue-mimetic matrices as instructive stem cell microenvironments
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DOI：
10.1038/nmeth.2523
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发表时间：
2013-08-01
期刊：
影响因子：
48
通讯作者：
Werner, Carsten
中科院分区：
文献类型：
--
作者：
Prewitz, Marina C.;Seib, F. Philipp;Werner, Carsten
确定细胞外基质（ECM）在干细胞龛中的确切作用的主要障碍是缺乏合适的体外方法来概括复杂的ECM微环境。在这里，我们描述了一种方法，允许可靠的锚定天然细胞分泌的ECM培养载体。我们通过制造两种类型的人骨髓特异性ECM基质来验证我们的方法，所述基质足够稳健以在体外支持人间充质干细胞（MSC）和造血干细胞和祖细胞。我们表征了MSC衍生的ECM制剂的分子组成、结构特征和纳米力学性质，并证明了它们支持骨髓干细胞扩增和分化的能力。我们的方法能够破译和调制组织驻留干细胞的天然样多组分ECM，因此将为更合理的工程干细胞龛设计奠定基础。
A major obstacle in defining the exact role of extracellular matrix (ECM) in stem cell niches is the lack of suitable in vitro methods that recapitulate complex ECM microenvironments. Here we describe a methodology that permits reliable anchorage of native cell-secreted ECM to culture carriers. We validated our approach by fabricating two types of human bone marrow-specific ECM substrates that were robust enough to support human mesenchymal stem cells (MSCs) and hematopoietic stem and progenitor cells in vitro. We characterized the molecular composition, structural features and nanomechanical properties of the MSC-derived ECM preparations and demonstrated their ability to support expansion and differentiation of bone marrow stem cells. Our methodology enables the deciphering and modulation of native-like multicomponent ECMs of tissue-resident stem cells and will therefore prepare the ground for a more rational design of engineered stem cell niches.