Chemotaxis and Differentiation of Human Adipose Tissue CD34⁺/CD31^- Progenitor Cells: Role of SDF-1 Released by Adipose Tissue Capillary Endothelial Cells

¹ AVENIR team, INSERM U858/I2MR, Paul Sabatier University, IFR31, Toulouse, France
² Institute of Cardiovascular Physiology, Johann Wolfgang Goethe University, Theodor-Stern Kai 7, 60590 Frankfurt am Main, Germany.

^* To whom correspondence should be addressed. E-mail: coralie.sengenes{at}toulouse.inserm.fr.

	Abstract

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 media 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, i.e. the stromal derived factor 1 (SDF-1). Finally, hAT-CECs induced the differentiation of hAT-CD34⁺/CD31^- cells toward an 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-CECs-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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