title: Endogenous collagen influences differentiation of human multipotent mesenchymal stromal cells.
abstract: Human multipotent mesenchymal stromal cells (hMSCs) are multipotent cells that, in the presence of appropriate stimuli, can differentiate into different lineages such as the osteogenic, chondrogenic, and adipogenic lineages. In the presence of ascorbic acid, MSCs secrete an extracellular matrix mainly composed of collagen type I. Here we assessed the potential role of endogenous collagen synthesis in hMSC differentiation and stem cell maintenance. We observed a sharp reduction in proliferation rate of hMSCs in the absence of ascorbic acid, concomitant with a reduction in osteogenesis in vitro and bone formation in vivo. In line with a positive role for collagen type I in osteogenesis, gene expression profiling of hMSCs cultured in the absence of ascorbic acid demonstrated increased expression of genes involved in adipogenesis and chondrogenesis and a reduction in expression of osteogenic genes. We also observed that matrix remodeling and anti-osteoclastogenic signals were high in the presence of ascorbic acid. The presence of collagen type I during the expansion phase of hMSCs did not affect their osteogenic and adipogenic differentiation potential. In conclusion, the collagenous matrix supports both proliferation and differentiation of osteogenic hMSCs but, on the other hand, presents signals stimulating matrix remodeling and inhibiting osteoclastogenesis.
authors.affiliation: Department of Tissue Regeneration, University of Twente, Enschede, The Netherlands.
authors.forename: Hugo
authors.initials: H
authors.lastname: Fernandes
authors.forename: Anouk
authors.initials: A
authors.lastname: Mentink
authors.forename: Ruud
authors.initials: R
authors.lastname: Bank
authors.forename: Reinout
authors.initials: R
authors.lastname: Stoop
authors.forename: Clemens
authors.initials: C
authors.lastname: van Blitterswijk
authors.forename: Jan
authors.initials: J
authors.lastname: de Boer
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002828:Choristoma / Q000473:pathology; D003094:Collagen / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D010641:Phenotype; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
chemical_list: D003094:Collagen; D001205:Ascorbic Acid