Clinical Hemorheology and Microcirculation 48 (2011) 5–13 DOI 10.3233/CH-2011-1397 IOS Press 5 Angiogenesis: The role of PDGF-BB on Adiopse-tissue derived Stem Cells (ASCs) Sebastian Gehmert a,b,d , Sanga Gehmert c,d , Mulyadi Hidayat a,b , Maitham Sultan a,b , Arne Berner a,b , Silvan Klein a,b,d , Johannes Zellner a,b , Michael M ¨ uller a,b and Lukas Prantl a,b,d,∗ a Center of Plastic and Reconstructive Surgery, University Medical Center Regensburg, Regensburg, Germany b Department of Trauma Surgery, University Medical Center Regensburg, Regensburg, Germany c Department of Obstetrics and Gynecology, University Medical Center Regensburg, Regensburg, Germany d Department of Molecular Pathology, The University of Texas, MD, Anderson Cancer Center, Houston, TX, USA Abstract. Recently, it was shown that mesenchymal stem cells (MSCs) are capable of differentiating into endothelial cells which highlights the potential role of MSCs in neovascularization. In the present study, we investigated the paracrine factors responsible for tube formation in human adipose-tissue derived stem cells (ASCs). Moreover, we analyzed ASC’s migration towards PDGF- BB and altered levels of proteins involved in different pathways. Freshly isolated human adipose tissue-derived stem cells were seeded onto wells coated with Matrigel and cultured in endothelial growth medium. Capillary-like tube formation was observed after 18 hours culture. Tube formation was significantly reduced in the presence of antibodies against platelet-derived growth factor receptor beta (PDGF) or basic fibroblast growth factor (bFGF). Reverse phase proteomic assay (RPPA) was used to interrogate the expression of 139 phosphorylated or native proteins after incubation with PDGF-BB protein for 24 hours. The present data suggest, that freshly isolated ASCs contain a subpopuplation of stem cells that can form capillary like tubes which is dependent on PDGF and bFGF signaling pathway. Furthermore, Migration of human ASCs significantly increased in response to increased concentrations of PDGF-BB. In addition, incubation of ASCs with PDGF-BB altered phosphorylation of several transcription proteins that are widely expressed throughout the hematopoietic system, targeting genes that have been associated with proliferation, anti-apoptosis or differentiation. Keywords: Angiogenesis, adipose-tissue derived stem cells, PDGF-BB, endothelial differentiation, migration 1. Introduction Angiogenesis is a very tight controlled process governed by a fine balance between angiogenetic and antiangiogenetic factors [3, 17, 22]. To date migration and proliferation of endothelial progenitor cells has been shown to be involved in this process. Furthermore, motility of pericytes is enhanced during vascular development due to endothelial cells that secret proteins and form a chemotaxis-like gradient in order to recruit pericyctes [11, 14]. PDGF-BB/PDGF- signaling plays an important role in vascular maturation and has been well-documented by genetic studies. Recently, several studies have correlated PDGF-BB signaling with vascular remodeling and shown that transgenic PDGF-BB expression can increase pericyte ∗ Corresponding author. E-mail: lukas.prantl@klinik.uni-regensburg.de. 1386-0291/11/$27.50 © 2011 – IOS Press and the authors. All rights reserved