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TGFβ-dependent epithelial-to-mesenchymal transition is required to generate cardiospheres from human adult heart biopsies

Authors :
Ann Zeuner
Mark Mercola
Alessandro Giacomello
Francesco Angelini
Fabio Miraldi
Isotta Chimenti
Elisa Messina
Elvira Forte
Department of Molecular Medicine
Institut Pasteur, Fondation Cenci Bolognetti - Istituto Pasteur Italia, Fondazione Cenci Bolognetti
Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome]
Department of Cardiovascular Physiopathology, Anesthesiology and General Surgery
Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome]
Department of Biotechnology and Medical - Surgical Sciences
Hematology, Oncology and Molecular Medicine
Istituto Superiore di Sanita [Rome]
Sanford Burnham Medical Research Institute
La Jolla
Source :
Stem Cells and Development, Stem Cells and Development, Mary Ann Liebert, 2012, 21 (17), pp.3081-90. ⟨10.1089/scd.2012.0277⟩
Publication Year :
2012
Publisher :
HAL CCSD, 2012.

Abstract

International audience; Autologous cardiac progenitor cells (CPCs) isolated as cardiospheres (CSps) represent a promising candidate for cardiac regenerative therapy. A better understanding of the origin and mechanisms underlying human CSps formation and maturation is undoubtedly required to enhance their cardiomyogenic potential. Epithelial-to-mesenchymal transition (EMT) is a key morphogenetic process that is implicated in the acquisition of stem cell-like properties in different adult tissues, and it is activated in the epicardium after ischemic injury to the heart. We investigated whether EMT is involved in the formation and differentiation of human CSps, revealing that an up-regulation of the expression of EMT-related genes accompanies CSps formation that is relative to primary explant-derived cells and CSp-derived cells grown in a monolayer. EMT and CSps formation is enhanced in the presence of transforming growth factor β1 (TGFβ1) and drastically blocked by the type I TGFβ-receptor inhibitor SB431452, indicating that TGFβ-dependent EMT is essential for the formation of these niche-like 3D-multicellular clusters. Since TGFβ is activated in the myocardium in response to injury, our data suggest that CSps formation mimics an adaptive mechanism that could potentially be enhanced to increase in vivo or ex vivo regenerative potential of adult CPCs.

Details

Language :
English
ISSN :
15473287
Database :
OpenAIRE
Journal :
Stem Cells and Development, Stem Cells and Development, Mary Ann Liebert, 2012, 21 (17), pp.3081-90. ⟨10.1089/scd.2012.0277⟩
Accession number :
edsair.doi.dedup.....138f946af331f34f681163363b9ed600