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Tightly anchored tissue-mimetic matrices as instructive stem cell microenvironments
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Tightly anchored tissue-mimetic matrices as instructive stem cell microenvironments
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Journal Article
Tightly anchored tissue-mimetic matrices as instructive stem cell microenvironments
2013
Overview
A method to tightly attach cell-derived extracellular matrix (ECM) to the culture surface is described. It is applied to generate bone marrow mesenchymal stem cell–derived ECM, which supports culture of human hematopoietic stem and progenitor cells.
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.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ Animals
/ Biomedical Engineering/Biotechnology
/ Bone Marrow Cells - cytology
/ Bone Marrow Cells - physiology
/ Cell Differentiation - physiology
/ Extracellular Matrix - physiology
/ Hematopoietic Stem Cells - cytology
/ Hematopoietic Stem Cells - physiology
/ Humans
/ Mesenchymal Stromal Cells - cytology
/ Mesenchymal Stromal Cells - physiology
/ Mice
/ Microscopy, Electron, Scanning
/ Proteins
/ Specific Pathogen-Free Organisms
