Tightly anchored tissue-mimetic matrices as instructive stem cell microenvironments

Prewitz, Marina and Seib, F Philipp and von Bonin, Malte and Friedrichs, Jens and Stißel, Aline and Niehage, Christian and Müller, Katrin and Anastassiadis, Konstantinos and Waskow, Claudia and Hoflack, Bernard and Bornhäuser, Martin and Werner, Carsten (2013) Tightly anchored tissue-mimetic matrices as instructive stem cell microenvironments. Nature Methods, 10 (8). 788–794. ISSN 1548-7091

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Abstract

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.