title: Space constraints govern fate of hematopoietic stem and progenitor cells in vitro.
abstract: Deciphering exogenous cues that determine stem cell fate decisions is a persisting challenge of cell biology and bioengineering. In an effort to unravel the role of spatial constraints in the cell-instructive characteristics of bone marrow microenvironments, murine hematopoietic stem and progenitor cells (HSPC) were exposed to fibronectin-coated microcavities in vitro. Microcavity sizes were chosen to allow for the inclusion of either individual or multiple cells. Repopulation experiments using lethally irradiated mice showed that the maintenance of functional HSPC in culture critically depends on cavity dimensions. Short-term repopulating hematopoietic stem cells (ST-HSC) were found to be best supported within single-cell sized compartments while long-term repopulating HSC (LT-HSC) were maintained within both cavity sizes. In sum, the reported data reveal spatial restriction to be a simple but powerful means for directing HSPC fate ex vivo.
authors.affiliation: Max Bergmann Center of Biomaterials, Leibniz Institute of Polymer Research Dresden, Hohe Strasse 6, 01069 Dresden, Germany.
authors.forename: Eike
authors.initials: E
authors.lastname: Müller
authors.affiliation: Regeneration in Hematopoiesis and Animal Models in Hematopoiesis, Institute for Immunology, Technische Universität Dresden, Fetschertrasse 74, 01307 Dresden, Germany.
authors.forename: Tatyana
authors.initials: T
authors.lastname: Grinenko
authors.affiliation: Max Bergmann Center of Biomaterials, Leibniz Institute of Polymer Research Dresden, Hohe Strasse 6, 01069 Dresden, Germany; Institute of Biochemistry, Universität Leipzig, Johannisallee 21, 04103 Leipzig, Germany.
authors.forename: Tilo
authors.initials: T
authors.lastname: Pompe
authors.affiliation: Regeneration in Hematopoiesis and Animal Models in Hematopoiesis, Institute for Immunology, Technische Universität Dresden, Fetschertrasse 74, 01307 Dresden, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Waskow
authors.affiliation: Max Bergmann Center of Biomaterials, Leibniz Institute of Polymer Research Dresden, Hohe Strasse 6, 01069 Dresden, Germany. Electronic address: werner@ipfdd.de.
authors.forename: Carsten
authors.initials: C
authors.lastname: Werner
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D005353:Fibronectins; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D005353:Fibronectins
keywords: ECM; In vivo test; Microstructure; Stem cell