Please use this identifier to cite or link to this item: https://doi.org/10.1089/scd.2008.0157
Title: Heparan sulfate mediates the proliferation and differentiation of rat mesenchymal stem cells
Authors: Dombrowski, C.
Song, S.J.
Chuan, P.
Lim, X.
Susanto, E.
Sawyer, A.A.
Woodruff, M.A. 
Hutmacher, D.W.
Nurcombe, V.
Cool, S.M.
Issue Date: 1-May-2009
Source: Dombrowski, C., Song, S.J., Chuan, P., Lim, X., Susanto, E., Sawyer, A.A., Woodruff, M.A., Hutmacher, D.W., Nurcombe, V., Cool, S.M. (2009-05-01). Heparan sulfate mediates the proliferation and differentiation of rat mesenchymal stem cells. Stem Cells and Development 18 (4) : 661-670. ScholarBank@NUS Repository. https://doi.org/10.1089/scd.2008.0157
Abstract: The growth and differentiation of mesenchymal stem cells (MSCs) is controlled by various growth factors, the activities of which can be modulated by heparan sulfates (HSs). We have previously noted the necessity of sulfated glycosaminoglycans for the fibroblast growth factor type 2 (FGF-2)-stimulated differentiation of osteoprogenitor cells. Here we show that exogenous application of HS 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 rat bone marrow stem cells (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. 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. Blocking FGFR1 signaling in postconfluent osteogenic cultures significantly increased calcium deposition. Taken together our data suggest that FGFR1 signaling plays an important role during osteogenic differentiation, first by stimulating cell growth that is closely followed by an inhibitory effect once the cells have reached confluence. It also confirms the importance of HS as a coreceptor 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. © 2009 Mary Ann Liebert, Inc.
Source Title: Stem Cells and Development
URI: http://scholarbank.nus.edu.sg/handle/10635/67079
ISSN: 15473287
DOI: 10.1089/scd.2008.0157
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.

SCOPUSTM   
Citations

55
checked on Dec 6, 2017

WEB OF SCIENCETM
Citations

49
checked on Nov 18, 2017

Page view(s)

36
checked on Dec 10, 2017

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.