title: Tightly anchored tissue-mimetic matrices as instructive stem cell microenvironments.
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.
authors.affiliation: Leibniz Institute of Polymer Research Dresden, Max Bergmann Center of Biomaterials, Dresden, Germany.
authors.forename: Marina C
authors.initials: MC
authors.lastname: Prewitz
authors.forename: F Philipp
authors.initials: FP
authors.lastname: Seib
authors.forename: Malte
authors.initials: M
authors.lastname: von Bonin
authors.forename: Jens
authors.initials: J
authors.lastname: Friedrichs
authors.forename: Aline
authors.initials: A
authors.lastname: Stißel
authors.forename: Christian
authors.initials: C
authors.lastname: Niehage
authors.forename: Katrin
authors.initials: K
authors.lastname: Müller
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Anastassiadis
authors.forename: Claudia
authors.initials: C
authors.lastname: Waskow
authors.forename: Bernard
authors.initials: B
authors.lastname: Hoflack
authors.forename: Martin
authors.initials: M
authors.lastname: Bornhäuser
authors.forename: Carsten
authors.initials: C
authors.lastname: Werner
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology*; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000502:physiology; D005109:Extracellular Matrix / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D018625:Microscopy, Atomic Force; D008855:Microscopy, Electron, Scanning; D013047:Specific Pathogen-Free Organisms; D055153:Stem Cell Niche / Q000502:physiology*