Effect of Hypoxia on Gene Expression of Bone Marrow-derived Mesenchymal Stem Cells and Mononuclear Cells

¹ Department of Regenerative Medicine and Tissue Engineering, National Cardiovascular Center Research Institute, Osaka, Japan
² GeneticLab Co., Ltd., Sapporo, Japan
³ Department of Cardiovascular Surgery, National Cardiovascular Center, Osaka, Japan

^* To whom correspondence should be addressed. E-mail: sonishi{at}ri.ncvc.go.jp.

	Abstract

Mesenchymal stem cells (MSC) have self-renewal and multi-lineage differentiation potential including differentiation into endothelial cells and vascular smooth muscle cells. Although bone marrow-derived mononuclear cells (MNC) have been applied for therapeutic angiogenesis in ischemic tissue, little information is available regarding comparison of the molecular foundation between MNC and their MSC subpopulation, as well as their response to ischemic conditions. Thus, we investigated the gene expression profiles between MSC and MNC of rat bone marrow under normoxia and hypoxia using a microarray containing 31,099 genes. In normoxia, 2232 (7.2%) and 2193 genes (7.1%) were preferentially expressed more than threefold in MSC and MNC, respectively, and MSC expressed a number of genes involved in development, morphogenesis, cell adhesion and proliferation, whereas various genes highly expressed in MNC were involved in inflammatory response and chemotaxis. Under hypoxia, 135 (0.44%) and 49 (0.16%) genes were upregulated (> threefold) in MSC and MNC, respectively, and a large number of those upregulated genes were involved in glycolysis and metabolism. Focusing on genes encoding secretory proteins, the upregulated genes in MSC under hypoxia included several molecules involved in cell proliferation and survival such as vascular endothelial growth factor-D, placenta growth factor, pre-B-cell colony enhancing factor 1, heparin binding epidermal growth factor-like growth factor and matrix metalloproteinase-9, while the upregulated genes in MNC under hypoxia included proinflammatory cytokines such as chemokine (C-X-C motif) ligand 2 and interleukin-1. Our results may provide information on the differential molecular mechanisms regulating the properties of MSC and MNC under ischemic conditions.

This article has been cited by other articles:

				M. Gnecchi, Z. Zhang, A. Ni, and V. J. Dzau Paracrine Mechanisms in Adult Stem Cell Signaling and Therapy Circ. Res., November 21, 2008; 103(11): 1204 - 1219. [Abstract] [Full Text] [PDF]

				J. S. Burchfield, M. Iwasaki, M. Koyanagi, C. Urbich, N. Rosenthal, A. M. Zeiher, and S. Dimmeler Interleukin-10 From Transplanted Bone Marrow Mononuclear Cells Contributes to Cardiac Protection After Myocardial Infarction Circ. Res., July 18, 2008; 103(2): 203 - 211. [Abstract] [Full Text] [PDF]