Epithelial-to-Mesenchymal Transition Enhances the Cardioprotective Capacity of Human Amniotic Epithelial Cells


<jats:p> The amniotic epithelium consists of cells exhibiting mature epitelial cell characteristics, but also varying degrees of stemness. We tested the hypothesis that induction of epithelial-to-mesenchymal transition (EMT) in amniotic epitelial cells (AECs) derived from human placenta enhances their capacity to support the ischemic myocardium. In response to incubation with transforming growth factor-β1 (TGF-β1) protein, AECs lost their cobblestone morphology and acquired a fibroblastoid shape, associated with downregulation of E-cadherin, upregulation of N-cadherin, Akt phosphorylation, and intracellular periostin translocation. EMT—AECs displayed greatly enhanced mobility and secreted gelatinase activity compared with naive AECs. The surface presentation of CD105 and CD73 decreased, and RNA microarray analysis mirrored the loss of epithelial characteristics and transcriptional profile. Unmodified AECs and EMT—AECs were then injected intramyocardially in fully immunocompetent mice after permanent LAD ligation, and heart function was followed by MRI as well as 2D speckle tracking echocardiography after 4 weeks. EMT—AEC-treated infarct hearts displayed better global systolic function and improved longitudinal strain rate in the area of interest. Although no signals of human cells were detectable by histology, infarct size was smaller in EMT—AEC-treated hearts, associated with fewer TUNEL-positive cells and upregulation of periostin, while blood vessel density was increased in both ACE- and EMT—AEC-treated hearts. We conclude that EMT enhances the cardioprotective effects of human AECs. </jats:p>






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Publication Info

Roy, Rajika, Marian Kukucka, Daniel Messroghli, Désirée Kunkel, Andreja Brodarac, Kristin Klose, Sven Geißler, Peter Moritz Becher, et al. (2015). Epithelial-to-Mesenchymal Transition Enhances the Cardioprotective Capacity of Human Amniotic Epithelial Cells. Cell Transplantation, 24(6). pp. 985–1002. 10.3727/096368913x675151 Retrieved from https://hdl.handle.net/10161/28946.

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Rajika Roy

Assistant Professor in Surgery

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