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INTRODUCTION: IFATS COLLECTION: THE STEM CELL NICHE

IFATS Collection: Adipose Stromal Cell Differentiation Is Reduced by Endothelial Cell Contact and Paracrine Communication: Role of Canonical Wnt Signaling

^aIndiana Center for Vascular Biology and Medicine,
^cMeridian Plastic Surgery Center, and
Departments of ^bCellular and Integrative Physiology,
^dMedical and Molecular Genetics, and
^eMedicine, Indiana University School of Medicine, Indianapolis, Indiana, USA

Key Words. Short interfering RNA • Wnt1 • Differentiation • Adipogenesis • Adult stem cells • Adipose stromal cells

Correspondence: Correspondence: Matthias Clauss, Ph.D., Indiana Center for Vascular Biology and Medicine, 975 West Walnut Street IB433, Indianapolis, Indiana 46202, USA. Telephone: 317-278-2837; Fax: 317-278-0089; e-mail: mclauss{at}iupui.edu; or Keith L. March, M.D., Ph.D., Indiana Center for Vascular Biology and Medicine, 975 West Walnut Street IB442, Indianapolis, Indiana 46202, USA. Telephone: 317-278-0130; Fax: 317-278-0089; e-mail: kmarch{at}iupui.edu

Received on March 27, 2008; accepted for publication on July 4, 2008.

First published online in STEM CELLS EXPRESS  July 31, 2008.

Adipose stromal cells (ASC) are multipotential mesenchymal progenitor cells that are readily induced to undergo adipogenic differentiation, and we have recently demonstrated them to have functional and phenotypic overlap with pericytes lining microvessels in adipose tissues. In this study we addressed the hypothesis that modulation of ASC fate within this perivascular niche can occur via interaction with endothelial cells (EC), which serve to modulate the adipogenic potential of ASC. To this end, we investigated contact as well as paracrine effects of EC on ASC adipogenesis, in two-dimensional coculture and via conditioned medium and analyzed mutual gene expression changes by real-time reverse transcription polymerase chain reaction (PCR). A significant decrease in adipogenic differentiation was observed in ASC when they were cocultured with EC but not control fibroblasts. This endothelial cell-specific effect was accompanied by increased expression of factors involved in Wnt signaling, most prominently Wnt1, Wnt4, and Wnt10a, which are well-known inhibitors of adipogenesis. Suppression of Wnt1 but not Wnt 10a or scrambled control short interfering RNA in cocultures partially reversed the endothelial cell effect, thus increasing adipogenic differentiation, suggesting a plausible role of Wnt1 ligand in modulation of adipogenesis by the vasculature. Furthermore, addition of recombinant Wnt ligand or the Wnt signaling agonist inhibited adipogenic differentiation of ASC in the absence of EC. In conclusion, these data define the relationship in adipose tissue between ASC and EC in the perivascular niche, in which the latter act to repress adipogenesis, thereby stabilizing vasculature. It is tempting to speculate that abnormal endothelial function may be associated with pathologic derepression of adipogenesis.

Disclosure of potential conflicts of interest is found at the end of this article.