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TISSUE-SPECIFIC STEM CELLS |
aInstitut National de la Santé et de la Recherche Médicale, U858, AVENIR Team, I2MR, Paul Sabatier University, IFR31, Toulouse, France;
bInstitute of Cardiovascular Physiology, Johann Wolfgang Goethe University, Frankfurt am Main, Germany
Key Words. Human CD34+ cells • Stromal derived factor-1 • Endothelial differentiation • Chemotaxis • CXCR-4 • Matrigel Microvasculature • Progenitor cells
Correspondence: Coralie Sengenès, Ph.D., Team 1, "Vascular network, progenitor cells and immune cells from adipose tissue," Institut National de la Santé et de la Recherche Médicale U858/I2MR, BP84225, 31432 Toulouse Cedex 4, France. Telephone: +33 5 6114 5975; Fax: +33 5 6125 5116; e-mail: coralie.sengenes{at}toulouse.inserm.fr
Received on March 14, 2007;
accepted for publication on May 17, 2007.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLS EXPRESS May 24, 2007.
The native CD34+/CD31– cell population present in the stroma-vascular fraction of human adipose tissue (hAT) displays progenitor cell properties since they exhibit adipocyte- and endothelial cell-like phenotypes under appropriate stimuli. To analyze the signals within hAT regulating their phenotypes, the influence of hAT-derived capillary endothelial cells (CECs) was studied on the chemotaxis and differentiation of the hAT-CD34+/CD31– cells. Conditioned medium from hAT-CECs led to a strong chemotaxis of the hAT-CD34+/CD31– cells that was inhibited with pretreatments with pertussis toxin, CXCR-4 antagonist, or neutralizing antibodies. Furthermore, hAT-CECs produced and secreted the CXCR-4 ligand, that is, the stromal derived factor-1 (SDF-1). Finally, hAT-CECs induced the differentiation of hAT-CD34+/CD31– cells toward an endothelial cell (EC) phenotype. Indeed, hAT-CECs and -CD34+/CD31– cell coculture stimulated in a two-dimensional system the expression of the EC CD31 marker by the hAT-progenitor cells and, in a three-dimensional approach, the formation of capillary-like structures via a SDF-1/CXCR-4 dependent pathway. Thus, the migration and differentiation of hAT progenitor cells are modulated by hAT-CEC-derived factors. SDF-1, which is secreted by hAT-derived CECs, and its receptor CXCR-4, expressed by hAT-derived progenitor cells, may promote chemotaxis and differentiation of hAT-derived progenitor cells and thus contribute to the formation of the vascular network during the development of hAT.
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