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Heparan sulfate mediates the proliferation and differentiation of rat mesenchymal stem cells

Dombrowski, Christian , Song, Shu Jun , Chuan, Peiying , Lim, Xinhong , Susanto, Evelyn , Sawyer, Amber A. , Woodruff, Maria A., Hutmacher, Dietmar W., Nurcombe, Victor , & Cool, Simon M. (2009) Heparan sulfate mediates the proliferation and differentiation of rat mesenchymal stem cells. Stem Cells and Development, 18(4), pp. 661-670.

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Abstract

The growth and differentiation of mesenchymal stem cells is controlled by various growth factors, the activities of which can be modulated by heparan sulfates. We have previously underscored the necessity of sulfated glycosaminoglycans for the FGF-2-stimulated differentiation of osteoprogenitor cells. Here we show that exogenous application of heparan sulfate to cultures of primary rat MSCs stimulates their proliferation leading to increased expression of osteogenic markers and enhanced bone nodule formation. FGF-2 can also increase the proliferation and osteogenic differentiation of rMSCs when applied exogenously during their linear growth. However, as opposed to exogenous HS, the continuous use of FGF-2 during in vitro differentiation completely blocked rMSC mineralization. Furthermore, we show that the effects of both FGF-2 and HS are mediated through FGF receptor 1 (FGFR1) and that inhibition of signaling through this receptor arrests cell growth resulting in the cells being unable to reach the critical density necessary to induce differentiation. Interestingly, blocking FGFR1 signaling in post-confluent osteogenic cultures significantly increased calcium deposition. Taken together our data clearly suggests that FGFR1 signaling plays an important role during osteogenic differentiation, firstly by stimulating cell growth that is closely followed by an inhibitory affect once the cells have reached confluence. It also underlines the importance of HS as a co-receptor for the signaling of endogenous FGF-2 and suggests that purified glycosaminoglycans may be attractive alternatives to growth factors for improved ex vivo growth and differentiation of MSCs.

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22 citations in Web of Science®

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ID Code: 31246
Item Type: Journal Article
Additional URLs:
Keywords: mesenchymal stem cells
DOI: 10.1089/scd.2008.0157
ISSN: 1547-3287
Subjects: Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > BIOCHEMISTRY AND CELL BIOLOGY (060100) > Cell Development Proliferation and Death (060103)
Divisions: Past > QUT Faculties & Divisions > Faculty of Built Environment and Engineering
Current > Institutes > Institute of Health and Biomedical Innovation
Past > Schools > School of Engineering Systems
Copyright Owner: Copyright 2009 Mary Ann Liebert Inc.
Deposited On: 11 Mar 2010 08:20
Last Modified: 29 Feb 2012 23:50

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