title: Extracellular matrix deposition of bone marrow stroma enhanced by macromolecular crowding.
abstract: Decellularized extracellular matrices (ECM) from in vitro cell cultures can serve as in vivo-like matrix scaffolds for modulating cell-ECM interactions. Macromolecular crowding (MMC), the supplementation of synthetic or naturally occurring molecules resulting in excluded volume effects (EVE), has been demonstrated to provide valuable options for recapitulating the physiological environment of cells during matrix secretion. Human mesenchymal stem cell (MSC)-derived ECM was produced upon supplementation of standard culture medium with three different macromolecules of various size (10-500 kDa). Matrix secretion, ECM morphology and composition were compared for matrices obtained from crowded and non-crowded MSC cultures. In the context of generating functional stem cell niches, the MSC-derived bone marrow mimetic ECM scaffolds were tested for their supportive effect to maintain and expand human hematopoietic stem and progenitor cells (HSPC) in vitro. MMC in combination with metabolic stimulation of MSC was found to result in tissue-specific, highly organized ECM capable of retaining glycosaminoglycans and growth factors to effectively build in vitro microenvironments that support HSPC expansion.
authors.affiliation: Max Bergmann Center of Biomaterials Dresden, Leibniz Institute of Polymer Research Dresden, Hohe Strasse 6, 01069 Dresden, Germany.
authors.forename: Marina C
authors.initials: MC
authors.lastname: Prewitz
authors.affiliation: Max Bergmann Center of Biomaterials Dresden, Leibniz Institute of Polymer Research Dresden, Hohe Strasse 6, 01069 Dresden, Germany.
authors.forename: Aline
authors.initials: A
authors.lastname: Stißel
authors.affiliation: Max Bergmann Center of Biomaterials Dresden, Leibniz Institute of Polymer Research Dresden, Hohe Strasse 6, 01069 Dresden, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Friedrichs
authors.affiliation: Max Bergmann Center of Biomaterials Dresden, Leibniz Institute of Polymer Research Dresden, Hohe Strasse 6, 01069 Dresden, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Träber
authors.affiliation: Max Bergmann Center of Biomaterials Dresden, Leibniz Institute of Polymer Research Dresden, Hohe Strasse 6, 01069 Dresden, Germany; Center for Regenerative Therapies Dresden (CRTD), TU Dresden, Fetscherstrasse 105, 01307 Dresden, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Vogler
authors.affiliation: Center for Regenerative Therapies Dresden (CRTD), TU Dresden, Fetscherstrasse 105, 01307 Dresden, Germany; Medizinische Klinik I, University Hospital TU Dresden, Fetscherstrasse 74, 01307 Dresden, Germany. Electronic address: mc.prewitz@gmail.com.
authors.forename: Martin
authors.initials: M
authors.lastname: Bornhäuser
authors.affiliation: Max Bergmann Center of Biomaterials Dresden, Leibniz Institute of Polymer Research Dresden, Hohe Strasse 6, 01069 Dresden, Germany; Center for Regenerative Therapies Dresden (CRTD), TU Dresden, Fetscherstrasse 105, 01307 Dresden, Germany. Electronic address: carsten.werner@tu-dresden.de.
authors.forename: Carsten
authors.initials: C
authors.lastname: Werner
mesh_terms: D000328:Adult; D001854:Bone Marrow Cells / Q000166:cytology*; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D003094:Collagen / Q000737:chemistry; D003470:Culture Media / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D005353:Fibronectins / Q000737:chemistry; D006025:Glycosaminoglycans / Q000737:chemistry; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D037102:Lectins / Q000737:chemistry; D046911:Macromolecular Substances; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology; D018625:Microscopy, Atomic Force; D008854:Microscopy, Electron; D010012:Osteogenesis; D055153:Stem Cell Niche; D013234:Stem Cells / Q000166:cytology; D017154:Stromal Cells / Q000166:cytology*; D054457:Tissue Scaffolds; D055815:Young Adult
chemical_list: D003470:Culture Media; D005353:Fibronectins; D006025:Glycosaminoglycans; D036341:Intercellular Signaling Peptides and Proteins; D037102:Lectins; D046911:Macromolecular Substances; D003094:Collagen
keywords: Extracellular matrix; Hematopoietic stem cells; Macromolecular crowding; Mesenchymal stem cells