title: Amnion-derived mesenchymal stromal cells show angiogenic properties but resist differentiation into mature endothelial cells.
abstract: Mesenchymal stromal cells derived from the human amnion (hAMSC) currently play an important role in stem cell research, as they are multipotent cells that can be isolated using noninvasive methods and are immunologically tolerated in vivo. The objective of this study was to evaluate their endothelial differentiation potential with regard to a possible therapeutic use in vascular diseases. hAMSC were isolated from human term placentas and cultured in Dulbecco's modified Eagle's medium (DMEM) (non-induced hAMSC) or endothelial growth medium (EGM-2) (induced hAMSC). Induced hAMSC changed their fibroblast-like toward an endothelial-like morphology, and were able to take up acetylated low-density lipoprotein and form endothelial-like networks in the Matrigel assay. However, they did not express the mature endothelial cell markers von Willebrand factor and vascular endothelial-cadherin. Gene expression analysis revealed that induced hAMSC significantly downregulated pro-angiogenic genes such as tenascin C, Tie-2, vascular endothelial growth factor A (VEGF-A), CD146, and fibroblast growth factor 2 (FGF-2), whereas they significantly upregulated anti-angiogenic genes such as serpinF1, sprouty1, and angioarrestin. Analysis of protein expression confirmed the downregulation of FGF-2 and Tie-2 (27%±8% and 13%±1% of non-induced cells, respectively) and upregulation of the anti-angiogenic protein endostatin (226%±4%). Conditioned media collected from hAMSC enhanced viability of endothelial cells and had a stabilizing effect on endothelial network formation as shown by lactate dehydrogenase and Matrigel assay, respectively. In summary, endothelial induced hAMSC acquired some angiogenic properties but resisted undergoing a complete differentiation into mature endothelial cells by upregulation of anti-angiogenic factors. Nevertheless, they had a survival-enhancing effect on endothelial cells that might be useful in a variety of cell therapy or tissue-engineering approaches.
authors.affiliation: Institute of Cell Biology, Histology, and Embryology, Medical University of Graz, Graz, Austria.
authors.forename: Julia
authors.initials: J
authors.lastname: König
authors.forename: Berthold
authors.initials: B
authors.lastname: Huppertz
authors.forename: Gernot
authors.initials: G
authors.lastname: Desoye
authors.forename: Ornella
authors.initials: O
authors.lastname: Parolini
authors.forename: Julia D
authors.initials: JD
authors.lastname: Fröhlich
authors.forename: Gregor
authors.initials: G
authors.lastname: Weiss
authors.forename: Gottfried
authors.initials: G
authors.lastname: Dohr
authors.forename: Peter
authors.initials: P
authors.lastname: Sedlmayr
authors.forename: Ingrid
authors.initials: I
authors.lastname: Lang
mesh_terms: D000650:Amnion / Q000166:cytology*; D001681:Biological Assay; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D004338:Drug Combinations; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007797:Laminin / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000235:genetics; D010920:Placenta / Q000166:cytology; D011247:Pregnancy; D011509:Proteoglycans / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D015415:Biomarkers; D017077:Culture Media, Conditioned; D004338:Drug Combinations; D007797:Laminin; D008077:Lipoproteins, LDL; D011509:Proteoglycans; C032629:acetyl-LDL; C059485:matrigel; D003094:Collagen