Heparan sulfate enhances the self-renewal and therapeutic potential of mesenchymal stem cells from human adult bone marrow

Torben Helledie, Christian Dombrowski, Bina Rai, Zophia X.H. Lim, Ian Lee Hock Hin, David A. Rider, Gary S. Stein, Wanjin Hong, Andre J. Van Wijnen, James H. Hui, Victor Nurcombe, Simon M. Cool

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Insufficient cell number hampers therapies utilizing adult human mesenchymal stem cells (hMSCs) and current ex vivo expansion strategies lead to a loss of multipotentiality. Here we show that supplementation with an embryonic form of heparan sulfate (HS-2) can both increase the initial recovery of hMSCs from bone marrow aspirates and increase their ex vivo expansion by up to 13-fold. HS-2 acts to amplify a subpopulation of hMSCs harboring longer telomeres and increased expression of the MSC surface marker stromal precursor antigen-1. Gene expression profiling revealed that hMSCs cultured in HS-2 possess a distinct signature that reflects their enhanced multipotentiality and improved bone-forming ability when transplanted into critical-sized bone defects. Thus, HS-2 offers a novel means for decreasing the expansion time necessary for obtaining therapeutic numbers of multipotent hMSCs without the addition of exogenous growth factors that compromise stem cell fate.

Original languageEnglish (US)
Pages (from-to)1897-1910
Number of pages14
JournalStem Cells and Development
Volume21
Issue number11
DOIs
StatePublished - Jul 20 2012

ASJC Scopus subject areas

  • Hematology
  • Developmental Biology
  • Cell Biology

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    Helledie, T., Dombrowski, C., Rai, B., Lim, Z. X. H., Hin, I. L. H., Rider, D. A., Stein, G. S., Hong, W., Van Wijnen, A. J., Hui, J. H., Nurcombe, V., & Cool, S. M. (2012). Heparan sulfate enhances the self-renewal and therapeutic potential of mesenchymal stem cells from human adult bone marrow. Stem Cells and Development, 21(11), 1897-1910. https://doi.org/10.1089/scd.2011.0367