title: Glioblastoma-dependent differentiation and angiogenic potential of human mesenchymal stem cells in vitro.
abstract: Tumor angiogenesis is of central importance in the malignancy of glioblastoma multiforme (GBM). As previously shown, human mesenchymal stem cells (hMSC) migrate towards GBM and are incorporated into tumor microvessels. However, phenotype and function of recruited hMSC remain unclear. We evaluated the differentiation and angiogenic potential of hMSC after stimulation with glioblastoma-conditioned medium in vitro. Immunostaining with endothelial, smooth muscle cell and pericyte markers was used to analyze hMSC differentiation in different concentrations of tumor-conditioned medium (CM), and the angiogenic potential was evaluated by matrigel-based tube-formation assay (TFA). Immunofluorescence staining revealed that tumor-conditioned hMSC (CM-hMSC) expressed CD 151, VE-cadherin, desmin, α-smooth muscle actin, nestin, and nerval/glial antigen 2 (NG2) in a CM concentration-dependent manner, whereas no expression of von-Willebrand factor (vWF) and smooth myosin could be detected. These findings are indicative of GBM-dependent differentiation of hMSC into pericyte-like cells, rather than endothelial or smooth muscle cells. Furthermore, TFA of hMSC and CM-hMSC revealed CM-dependent formation of capillary-like networks, which differed substantially from those formed by human endothelial cells (HUVEC), also implying pericyte-like tube formation. These results are indicative of GBM-derived differentiation of hMSC into pericyte-like mural cells, which might contribute to the neovascularization and stabilization of tumor vessels.
authors.affiliation: Department of Neurology, Ludwig-Maximilians-University, Marchioninistr. 15, 81377 Munich, Germany. tobias.birnbaum@med.uni-muenchen.de
authors.forename: Tobias
authors.initials: T
authors.lastname: Birnbaum
authors.forename: Jenna
authors.initials: J
authors.lastname: Hildebrandt
authors.forename: Georg
authors.initials: G
authors.lastname: Nuebling
authors.forename: Petra
authors.initials: P
authors.lastname: Sostak
authors.forename: Andreas
authors.initials: A
authors.lastname: Straube
mesh_terms: D001932:Brain Neoplasms / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion; D002454:Cell Differentiation; D002465:Cell Movement; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004338:Drug Combinations; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D005909:Glioblastoma / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D066298:In Vitro Techniques; D007381:Intermediate Filament Proteins / Q000378:metabolism; D007797:Laminin / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000473:pathology*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D009389:Neovascularization, Pathologic; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D020286:Pericytes / Q000166:cytology / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned; D004338:Drug Combinations; D007381:Intermediate Filament Proteins; D007797:Laminin; C577484:NES protein, human; D009419:Nerve Tissue Proteins; D064231:Nestin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen