title: Angiogenesis: the role of PDGF-BB on adipose-tissue derived stem cells (ASCs).
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.
authors.affiliation: Center of Plastic and Reconstructive Surgery, University Medical Center Regensburg, Regensburg, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Gehmert
authors.forename: Sanga
authors.initials: S
authors.lastname: Gehmert
authors.forename: Mulyadi
authors.initials: M
authors.lastname: Hidayat
authors.forename: Maitham
authors.initials: M
authors.lastname: Sultan
authors.forename: Arne
authors.initials: A
authors.lastname: Berner
authors.forename: Silvan
authors.initials: S
authors.lastname: Klein
authors.forename: Johannes
authors.initials: J
authors.lastname: Zellner
authors.forename: Michael
authors.initials: M
authors.lastname: Müller
authors.forename: Lukas
authors.initials: L
authors.lastname: Prantl
mesh_terms: D000273:Adipose Tissue / Q000166:cytology* / Q000378:metabolism; D000077214:Becaplermin; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis / Q000494:pharmacology / Q000502:physiology*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000096:biosynthesis / Q000502:physiology; D050791:STAT Transcription Factors / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D000077214:Becaplermin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D020574:Proto-Oncogene Proteins c-sis; D020797:Receptor, Platelet-Derived Growth Factor beta; D050791:STAT Transcription Factors; D058570:TOR Serine-Threonine Kinases; C546842:MTOR protein, human