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Fibroblast growth factor-10 promotes cardiomyocyte differentiation from embryonic and induced pluripotent stem cells

Sunny Sun-Kin Chan1, Hui-Jing Li, Ying-Chang Hsueh

  • 1Institute of Clinical Medicine and Research Center for Clinical Medicine, National Cheng Kung University and Hospital, Tainan, Taiwan.

Plos One
|January 5, 2011
PubMed

Insights

Fibroblast growth factor-10 (FGF-10) promotes cardiomyocyte differentiation from both embryonic stem (ES) cells and induced pluripotent stem (iPS) cells. This discovery holds promise for future clinical applications in cardiac repair.

Area of Science:

  • Cardiovascular Biology
  • Stem Cell Research
  • Developmental Biology

Background:

  • The fibroblast growth factor (FGF) family plays a crucial role in heart development.
  • The specific role of FGFs in cardiomyocyte differentiation from stem cells remains understudied.

Purpose of the Study:

  • To investigate the mechanisms and characteristics of cardiomyocyte differentiation induced by FGF family proteins in embryonic stem (ES) cells and induced pluripotent stem (iPS) cells.

Main Methods:

  • Utilized mouse ES cells with an α-myosin heavy chain (αMHC) promoter-driven enhanced green fluorescent protein (EGFP) reporter and mouse iPS cells.
  • Assessed FGF expression patterns during differentiation, tested FGF-10's dose- and time-dependency, and employed neutralizing antibodies and receptor antagonists.
  • Analyzed gene expression changes via microarray and Gene Ontology analysis.
  • Evaluated FGF-10's effect on cardiomyocyte differentiation in vivo through intramyocardial co-administration with ES cells.

Main Results:

  • FGF-10 demonstrated a time- and concentration-dependent induction of cardiomyocyte differentiation from ES cells.
  • Inhibition of cardiomyocyte differentiation was observed with FGF-10 neutralizing antibodies, FGF receptor antagonist PD173074, and FGF-10/FGFR-2 specific shRNAs.
  • FGF-10 enhanced cardiomyocyte differentiation from iPS cells, an effect blocked by FGF-10 neutralizing antibody or PD173074.
  • Microarray analysis revealed upregulation of cardiac development genes following FGF-10 treatment.
  • In vivo studies confirmed FGF-10's promotion of cardiomyocyte differentiation when co-administered with ES cells.

Conclusions:

  • FGF-10 effectively induces cardiomyocyte differentiation from both ES and iPS cells.
  • These findings suggest FGF-10 has significant potential for clinical translation in regenerative medicine for cardiac conditions.
Abstract

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