Abstract
BackgroundThe fibroblast growth factor (FGF) family is essential to normal heart development. Yet, its contribution to cardiomyocyte differentiation from stem cells has not been systemically studied. In this study, we examined the mechanisms and characters of cardiomyocyte differentiation from FGF family protein treated embryonic stem (ES) cells and induced pluripotent stem (iPS) cells.Methodology/Principal FindingsWe used mouse ES cells stably transfected with a cardiac-specific α-myosin heavy chain (αMHC) promoter-driven enhanced green fluorescent protein (EGFP) and mouse iPS cells to investigate cardiomyocyte differentiation. During cardiomyocyte differentiation from mouse ES cells, FGF-3, -8, -10, -11, -13 and -15 showed an expression pattern similar to the mesodermal marker Brachyury and the cardiovascular progenitor marker Flk-1. Among them, FGF-10 induced cardiomyocyte differentiation in a time- and concentration-dependent manner. FGF-10 neutralizing antibody, small molecule FGF receptor antagonist PD173074 and FGF-10 and FGF receptor-2 short hairpin RNAs inhibited cardiomyocyte differentiation. FGF-10 also increased mouse iPS cell differentiation into cardiomyocyte lineage, and this effect was abolished by FGF-10 neutralizing antibody or PD173074. Following Gene Ontology analysis, microarray data indicated that genes involved in cardiac development were upregulated after FGF-10 treatment. In vivo, intramyocardial co-administration of FGF-10 and ES cells demonstrated that FGF-10 also promoted cardiomyocyte differentiation.Conclusion/SignificanceFGF-10 induced cardiomyocyte differentiation from ES cells and iPS cells, which may have potential for translation into clinical applications.
Highlights
Heart failure is a leading cause of morbidity and mortality throughout the world [1,2]
We focused on the expression pattern of fibroblast growth factor (FGF) during embryonic stem (ES)/induced pluripotent stem (iPS) cell differentiation and carried out experiments to explore the role of FGFs in cardiomyocyte differentiation
The major challenge of using ES cell-based cardiomyocyte replacement therapy is the inefficiency of the conventional protocol to generate cardiomyocytes [8,9]
Summary
Heart failure is a leading cause of morbidity and mortality throughout the world [1,2]. Stem cell therapy is an attractive approach for cardiomyocyte replacement. Mesenchymal stem cells [3], cardiac progenitor cells [4], embryonic stem (ES) cells [5], and induced pluripotent stem (iPS) cells [6] have been reported to be capable of cardiomyocyte differentiation. The conventional protocol using the hanging drop method to induce cardiac differentiation from ES cells or iPS cells is extremely inefficient [7,8,9], which is a severe obstacle to the use of ES/iPS cells for cardiomyocyte replacement therapy. Studies to dissect the molecular pathways mediating ES/iPS cell differentiation into the cardiomyocyte lineage are essential. We examined the mechanisms and characters of cardiomyocyte differentiation from FGF family protein treated embryonic stem (ES) cells and induced pluripotent stem (iPS) cells
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
