title: Serum supplemented culture medium masks hypertrophic phenotypes in human pluripotent stem cell derived cardiomyocytes.
abstract: It has been known for over 20 years that foetal calf serum can induce hypertrophy in cultured cardiomyocytes but this is rarely considered when examining cardiomyocytes derived from pluripotent stem cells (PSC). Here, we determined how serum affected cardiomyocytes from human embryonic- (hESC) and induced pluripotent stem cells (hiPSC) and hiPSC from patients with hypertrophic cardiomyopathy linked to a mutation in the MYBPC3 gene. We first confirmed previously published hypertrophic effects of serum on cultured neonatal rat cardiomyocytes demonstrated as increased cell surface area and beating frequency. We then found that serum increased the cell surface area of hESC- and hiPSC-derived cardiomyocytes and their spontaneous contraction rate. Phenylephrine, which normally induces cardiac hypertrophy, had no additional effects under serum conditions. Likewise, hiPSC-derived cardiomyocytes from three MYBPC3 patients which had a greater surface area than controls in the absence of serum as predicted by their genotype, did not show this difference in the presence of serum. Serum can thus alter the phenotype of human PSC derived cardiomyocytes under otherwise defined conditions such that the effects of hypertrophic drugs and gene mutations are underestimated. It is therefore pertinent to examine cardiac phenotypes in culture media without or in low concentrations of serum.
authors: Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands; Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
authors: Cheryl
authors: C
authors: Dambrot
authors: Stefan R
authors: SR
authors: Braam
authors: Leon G J
authors: LG
authors: Tertoolen
authors: Matthew
authors: M
authors: Birket
authors: Douwe E
authors: DE
authors: Atsma
authors: Christine L
authors: CL
authors: Mummery
mesh_terms: D000200:Action Potentials; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D002454:Cell Differentiation; D002478:Cells, Cultured; D003470:Culture Media / Q000737:chemistry*; D020405:Dermis / Q000166:cytology / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology / Q000502:physiology*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007091:Image Processing, Computer-Assisted; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000502:physiology*; D051379:Mice; D009154:Mutation / Q000235:genetics; D032383:Myocytes, Cardiac / Q000166:cytology / Q000502:physiology*; D010641:Phenotype; D051381:Rats; D044967:Serum / Q000737:chemistry*; D000099163:Myosin Binding Protein C
chemical_list: D002118:Calcium; D002352:Carrier Proteins; D003470:Culture Media; D000099163:Myosin Binding Protein C
keywords: cardiomyocytes; human pluripotent stem cells; hypertrophy; serum