Cardiac Differentiation of Adipose Tissue-Derived Stem Cells Is Driven by BMP4 and bFGF but Counteracted by 5-Azacytidine and Valproic Acid.
Adipose Tissue-Derived Stem Cells
BMP4
Basic Fibroblast Growth Factor
Cardiomyocyte
Small Molecules
Journal
Cell journal
ISSN: 2228-5806
Titre abrégé: Cell J
Pays: Iran
ID NLM: 101566618
Informations de publication
Date de publication:
Oct 2020
Oct 2020
Historique:
received:
14
12
2018
accepted:
14
07
2019
entrez:
22
12
2019
pubmed:
22
12
2019
medline:
22
12
2019
Statut:
ppublish
Résumé
Bone morphogenetic protein 4 (BMP4) and basic fibroblast growth factor (bFGF) play important roles in embryonic heart development. Also, two epigenetic modifying molecules, 5'-azacytidine (5'-Aza) and valproic acid (VPA) induce cardiomyogenesis in the infarcted heart. In this study, we first evaluated the role of BMP4 and bFGF in cardiac trans-differentiation and then the effectiveness of 5´-Aza and VPA in reprogramming and cardiac differentiation of human adipose tissue-derived stem cells (ADSCs). In this experimental study, human ADSCs were isolated by collagenase I digestion. For cardiac differentiation, third to fifth-passaged ADSCs were treated with BMP4 alone or a combination of BMP4 and bFGF with or without 5'-Aza and VPA pre-treatment. After 21 days, the expression of cardiac-specific markers was evaluated by reverse transcription polymerase chain reaction (RT-PCR), quantitative real-time PCR, immunocytochemistry, flow cytometry and western blot analyses. BMP4 and more prominently a combination of BMP4 and bFGF induced cardiac differentiation of human ADSCs. Epigenetic modification of the ADSCs by 5'-Aza and VPA significantly upregulated the expression of OCT4A, Our findings demonstrated the inductive role of BMP4 and especially BMP4 and bFGF combination in cardiac trans-differentiation of human ADSCs. Treatment with 5'-Aza and VPA reprogrammed ADSCs toward a more pluripotent state and increased tendency of the ADSCs for mesodermal differentiation. Although pre-treatment with 5'-Aza and VPA counteracted the cardiogenic effects of BMP4 and bFGF, it may be in favor of migration, engraftment and survival of the ADSCs after transplantation.
Identifiants
pubmed: 31863652
doi: 10.22074/cellj.2020.6582
pmc: PMC6947007
doi:
Types de publication
Journal Article
Langues
eng
Pagination
273-282Informations de copyright
Copyright© by Royan Institute. All rights reserved.
Déclaration de conflit d'intérêts
There is no conflict of interest in this study.
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