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  • 1.
    König, Julia
    et al.
    Institute of Cell Biology, Histology, and Embryology, Medical University of Graz, Graz, Austria.
    Huppertz, Berthold
    Institute of Cell Biology, Histology, and Embryology, Medical University of Graz, Graz, Austria.
    Desoye, Gernot
    Clinic of Obstetrics and Gynecology, Medical University of Graz, Graz, Austria.
    Parolini, Ornella
    Centro di Ricerca E. Menni, Fondazione Poliambulanza, Istituto Ospedaliero, Brescia, Italy.
    Fröhlich, Julia D
    Institute of Cell Biology, Histology, and Embryology, Medical University of Graz, Graz, Austria; Clinic of Obstetrics and Gynecology, Medical University of Graz, Graz, Austria.
    Weiss, Gregor
    Institute of Cell Biology, Histology, and Embryology, Medical University of Graz, Graz, Austria.
    Dohr, Gottfried
    Institute of Cell Biology, Histology, and Embryology, Medical University of Graz, Graz, Austria.
    Sedlmayr, Peter
    Institute of Cell Biology, Histology, and Embryology, Medical University of Graz, Graz, Austria.
    Lang, Ingrid
    Institute of Cell Biology, Histology, and Embryology, Medical University of Graz, Graz, Austria.
    Amnion-derived mesenchymal stromal cells show angiogenic properties but resist differentiation into mature endothelial cells2012In: Stem Cells and Development, ISSN 1547-3287, E-ISSN 1557-8534, Vol. 21, no 8, p. 1309-1320Article in journal (Refereed)
    Abstract [en]

    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.

  • 2.
    König, Julia
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Weiss, Gregor
    Institute of Cell Biology, Histology and Embryology, Medical University of Graz, Graz, Austria.
    Rossi, Daniele
    Centro di Ricerca E. Menni, Fondazione Poliambulanza, Brescia, Italy.
    Wankhammer, Karin
    Institute of Cell Biology, Histology and Embryology, Medical University of Graz, Graz, Austria .
    Reinisch, Andreas
    Stem Cell Research Unit, Division of Hematology, Department of Internal Medicine, Medical University of Graz, Graz, Austria..
    Kinzer, Manuela
    Institute of Cell Biology, Histology and Embryology, Medical University of Graz, Graz, Austria.
    Huppertz, Berthold
    Institute of Cell Biology, Histology and Embryology, Medical University of Graz, Graz, Austria..
    Pfeiffer, Dagmar
    Institute of Cell Biology, Histology and Embryology, Medical University of Graz, Graz, Austria..
    Parolini, Ornella
    Centro di Ricerca E. Menni, Fondazione Poliambulanza, Brescia, Italy.
    Lang, Ingrid
    Institute of Cell Biology, Histology and Embryology, Medical University of Graz, Graz, Austria..
    Placental Mesenchymal Stromal Cells Derived from Blood Vessels or Avascular Tissues: What Is the Better Choice to Support Endothelial Cell Function?2014In: Stem Cells and Development, ISSN 1547-3287, E-ISSN 1557-8534, Vol. 24, no 1, p. 115-131Article in journal (Refereed)
    Abstract [en]

    Mesenchymal stromal cells (MSCs) are promising tools for therapeutic revascularization of ischemic tissues and for support of vessel formation in engineered tissue constructs. Recently, we could show that avascular-derived MSCs from placental amnion release soluble factors that exhibit survival-enhancing effects on endothelial cells (ECs). We hypothesize that MSCs derived from placental blood vessels might have even more potent angiogenic effects. Therefore, we isolated and characterized MSCs from placental chorionic blood vessels (bv-MSCs) and tested their angiogenic potential in comparison to amnion-derived avascular MSCs (av-MSCs). bv-MSCs express a very similar surface marker profile compared with av-MSCs and could be differentiated toward the adipogenic and osteogenic lineages. bv-MSCs exert immunosuppressive properties on peripheral blood mononuclear cells, suggesting that they are suitable for cell transplantation settings. Conditioned medium (Cdm) from av-MSCs and bv-MSCs significantly enhanced EC viability, whereas only Cdm from bv-MSCs significantly increased EC migration and network formation (Matrigel assay). Angiogenesis array analysis of av- and bv-MSC-Cdm revealed a similar secretion pattern of angiogenic factors, including angiogenin, interleukins-6 and -8, and tissue inhibitors of matrix metalloproteinase-1 and 2. Enzyme-linked immunosorbent assay analysis showed that, in contrast to av-MSCs, bv-MSCs secreted vascular endothelial growth factor. In direct coculture with bv-MSCs, ECs showed a significantly increased formation of vessel-like structures compared with av-MSCs. With regard to therapeutic treatment, bv-MSCs and particularly their Cdm might be valuable to stimulate angiogenesis especially in ischemic tissues. av-MSCs and their Cdm could be beneficial in conditions when it is required to promote the survival and stabilization of blood vessels without the risk of unmeant angiogenesis.

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