title: TGFβ-dependent epithelial-to-mesenchymal transition is required to generate cardiospheres from human adult heart biopsies.
abstract: 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.
authors: Department of Molecular Medicine, Pasteur Institute-Cenci Bolognetti Foundation, Sapienza University of Rome, Rome, Italy.
authors: Elvira
authors: E
authors: Forte
authors: Fabio
authors: F
authors: Miraldi
authors: Isotta
authors: I
authors: Chimenti
authors: Francesco
authors: F
authors: Angelini
authors: Ann
authors: A
authors: Zeuner
authors: Alessandro
authors: A
authors: Giacomello
authors: Mark
authors: M
authors: Mercola
authors: Elisa
authors: E
authors: Messina
mesh_terms: D000328:Adult; D001549:Benzamides / Q000494:pharmacology; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D002454:Cell Differentiation; D002478:Cells, Cultured; D004149:Dioxoles / Q000494:pharmacology; D058750:Epithelial-Mesenchymal Transition; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D017202:Myocardial Ischemia / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors; D012038:Regeneration; D000071250:Snail Family Transcription Factors; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism* / Q000494:pharmacology
chemical_list: C459179:4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide; D001549:Benzamides; D015415:Biomarkers; D004149:Dioxoles; C497761:NOTCH1 protein, human; D051881:Receptor, Notch1; D018125:Receptors, Transforming Growth Factor beta; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D016212:Transforming Growth Factor beta