Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/61228
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Type: Journal article
Title: Enrichment for STRO-1 expression enhances the cardiovascular paracrine activity of human bone marrow-derived mesenchymal cell populations
Author: Psaltis, P.
Paton, S.
See, F.
Arthur, A.
Martin, S.
Itescu, S.
Worthley, S.
Gronthos, S.
Zannettino, A.
Citation: Journal of Cellular Physiology, 2010; 223(2):530-540
Publisher: Wiley-Liss
Issue Date: 2010
ISSN: 0021-9541
1097-4652
Statement of
Responsibility: 
P.J. Psaltis, S. Paton, F. See, A. Arthur, S. Martin, S. Itescu, S.G. Worthley, S. Gronthos and A.C.W. Zannettino
Abstract: The cardiovascular therapeutic potential of bone marrow mesenchymal stromal/stem cells (MSC) is largely mediated by paracrine effects. Traditional preparation of MSC has involved plastic adherence-isolation. In contrast, prospective immunoselection aims to improve cell isolation by enriching for mesenchymal precursor cells (MPC) at higher purity. This study compared the biological characteristics and cardiovascular trophic activity of plastic adherence-isolated MSC (PA-MSC) and MPC prepared from the same human donors by immunoselection for stromal precursor antigen-1 (STRO-1). Compared to PA-MSC, STRO-1-MPC displayed greater (1) clonogenicity, (2) proliferative capacity, (3) multilineage differentiation potential, and (4) mRNA expression of mesenchymal stem cell-related transcripts. In vitro assays demonstrated that conditioned medium from STRO-1-MPC had greater paracrine activity than PA-MSC, with respect to cardiac cell proliferation and migration and endothelial cell migration and tube formation. In keeping with this, STRO-1-MPC exhibited higher gene and protein expression of CXCL12 and HGF. Inhibition of these cytokines attenuated endothelial tube formation and cardiac cell proliferation, respectively. Paracrine responses were enhanced by using supernatant from STRO-1(Bright) MPC and diminished with STRO-1(Dim) conditioned medium. Together, these findings indicate that prospective isolation gives rise to mesenchymal progeny that maintain a higher proportion of immature precursor cells compared to traditional plastic adherence-isolation. Enrichment for STRO-1 is also accompanied by increased expression of cardiovascular-relevant cytokines and enhanced trophic activity. Immunoselection thus provides a strategy for improving the cardiovascular reparative potential of mesenchymal cells.
Keywords: Bone Marrow Cells; Cells, Cultured; Endothelial Cells; Myocytes, Cardiac; Multipotent Stem Cells; Humans; Cardiovascular Diseases; Plastics; RNA, Messenger; Biological Markers; Antigens, Surface; Culture Media, Conditioned; Mesenchymal Stem Cell Transplantation; Cell Culture Techniques; Immunomagnetic Separation; Colony-Forming Units Assay; Regeneration; Cell Adhesion; Paracrine Communication; Cell Differentiation; Cell Proliferation; Cell Movement; Mesenchymal Stromal Cells
Rights: Copyright © 2010 Wiley-Liss, Inc.
RMID: 0020096362
DOI: 10.1002/jcp.22081
Appears in Collections:Medicine publications

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