Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
König, J.
Endothelial differentiation potential of amnion-derived mesenchymal stromal cells
[ Dissertation ] Medical University of Graz, 2011. pp. 67
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- Autor*innen der Med Uni Graz:
- König Julia Maria
- Betreuer*innen:
- Desoye Gernot
- Huppertz Berthold
- Lang-Olip Ingrid
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- Abstract:
- Mesenchymal stromal cells derived from the amnion (hAMSC) currently play an important role in stem cell research, as they are multipotent cells which can be isolated using non-invasive 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 DMEM (non-induced hAMSC) or endothelial cell medium EGM-2 (induced hAMSC). Induced hAMSC changed their fibroblast-like morphology towards an endothelial-like morphology, and were able to take up acetylated LDL and form endothelial-like networks in the Matrigel assay. However, they did not express the mature endothelial cell markers vWF and VE-cadherin. Gene expression analysis revealed that induced hAMSC significantly downregulated pro-angiogenic genes such as tenascin C, Tie-2, VEGF A, CD146 and FGF-2, while they significantly upregulated anti angiogenic genes such as serpinF1, sprouty1 and angioarrestin. Analysis of protein expression confirmed 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%). Co-culture with hAMSC promoted formation of vessel-like structures by endothelial cells in vitro. In addition, conditioned media collected from hAMSC enhanced viability of endothelial cells and had a stabilizing effect on endothelial network formation as shown by LDH and Matrigel assay, respectively. This suggests a pericyte-like function of hAMSC and we could further demonstrate that hAMSC express the pericyte marker NG2 in situ and in vitro. 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 which might be useful in a variety of cell therapy or tissue engineering approaches.