P341	Vascular endothelial growth factor is increased by inflammatory cytokines Interleukin-6 and Oncostatin M in human adipose tissue-derived stem cells.
1G.Rega, 1Chr.Kaun, 1T.Weiss, 1Ph.Hohensinner, 1S.Demyanets, 2R.Roehle, 3M.Frey, 1G.Maurer, 4K.Huber, 1J.Wojta
1Department of Internal Medicine II, Medical University Vienna, Vienna, AT; 2Department of Surgery, Wilhelminenspital, Vienna, AT; 3Department of Surgery, Medical University Vienna, Vienna, AT; 43rd Department of Medicine, Wilhelminenspital, Vienna, AT.

Background: Adipose tissue is increasingly recognised for its angiogenic properties and recent studies suggest a role for adipose tissue-derived stem cells in therapeutic angiogenesis. Using stem cells derived from adipose tissue for treatment of cardiovascular ischemia it is of major interest how these cells respond to environmental conditions after cell delivery. Although several reports indicate that vascular endothelial growth factor (VEGF) accounts for most of the angiogenic activity of adipose tissue, its regulation has been poorly examined. Elevated levels of the glycoprotein 130 (gp130) ligand interleukin-6 (IL-6) are found after myocardial infarction and in patients with peripheral artery disease. The aim of our study was to investigate the impact of the gp130 ligands IL-6 and oncostatin M (OSM) on VEGF expression in human adipose tissue-derived stem cells. Methods: Stromal-vascular fraction (SVF) cells were prepared by collagenase digestion of human subcutaneous and omental adipose tissue and characterized by flow cytometry. CD34+ cells were isolated by magnetic microbeads from SVF cells. CD34+ cells were treated with IL-6 (100ng/ml) and OSM (100ng/ml), respectively, for 48h. VEGF antigen in supernatants was quantified by ELISA, mRNA levels were determined by RealTimePCR. Results: The freshly harvested SVF of human subcutaneous and omental adipose tissue contained large numbers of CD34+ cells. 75% of the subcutaneous SVF cells were CD34+ and 78% of the omental SVF cells expressed CD34. IL-6 significantly up-regulated VEGF production in CD34+ cells of subcutaneous and omental adipose tissue up to 3-fold and 4-fold, respectively. In subcutaneous and omental CD34+ cells OSM also significantly increased VEGF production up to 4-fold and 6-fold, respectively. These results were confirmed by RT-PCR on the level of specific mRNA expression. Conclusion: We could show that selected gp130 ligands significantly upregulate VEGF expression in CD34+ cells of human adipose tissue. If these effects are also operative in vivo one could hypothesize that elevated levels of gp130 ligands such as IL-6 seen after myocardial infarction could promote neovascularization through upregulation of VEGF in adipose tissue-derived stem cells after cell transplantation.

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