Roy, Rajika, Kukucka, Marian ORCID: 0000-0001-6201-1600, Messroghli, Daniel, Kunkel, Desiree, Brodarac, Andreja, Klose, Kristin, Geissler, Sven ORCID: 0000-0002-8750-6324, Becher, Peter Moritz, Kang, Sung Keun, Choi, Yeong-Hoon and Stamm, Christof (2015). Epithelial-to-Mesenchymal Transition Enhances the Cardioprotective Capacity of Human Amniotic Epithelial Cells. Cell Transplant., 24 (6). S. 985 - 1003. PUTNAM VALLEY: COGNIZANT COMMUNICATION CORP. ISSN 1555-3892

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Abstract

The amniotic epithelium consists of cells exhibiting mature epithelial cell characteristics, but also varying degrees of sternness. We tested the hypothesis that induction of epithelial-to-mesenchymal transition (EMT) in amniotic epithelial cells (AECs) derived from human placenta enhances their capacity to support the ischemic myocardium. In response to incubation with transforming growth factor-beta 1 (TGF-beta 1) protein, ABCs 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 ABCs. 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 ABCs.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Roy, RajikaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kukucka, MarianUNSPECIFIEDorcid.org/0000-0001-6201-1600UNSPECIFIED
Messroghli, DanielUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kunkel, DesireeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brodarac, AndrejaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klose, KristinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Geissler, SvenUNSPECIFIEDorcid.org/0000-0002-8750-6324UNSPECIFIED
Becher, Peter MoritzUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kang, Sung KeunUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Choi, Yeong-HoonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stamm, ChristofUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-416404
DOI: 10.3727/096368913X675151
Journal or Publication Title: Cell Transplant.
Volume: 24
Number: 6
Page Range: S. 985 - 1003
Date: 2015
Publisher: COGNIZANT COMMUNICATION CORP
Place of Publication: PUTNAM VALLEY
ISSN: 1555-3892
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
GROWTH-FACTOR-BETA; MYOCARDIAL-INFARCTION; STEM-CELLS; IN-VIVO; PERIOSTIN; DIFFERENTIATION; TRANSPLANTATION; EMT; INTERLEUKIN-8; EXPRESSIONMultiple languages
Cell & Tissue Engineering; Medicine, Research & Experimental; TransplantationMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/41640

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