Open AccessSerum supplemented culture medium masks hypertrophic phenotypes in human pluripotent stem cell derived cardiomyocytes
Author(s) -
Dambrot Cheryl,
Braam Stefan R.,
Tertoolen Leon G. J.,
Birket Matthew,
Atsma Douwe E.,
Mummery Christine L.
Publication year - 2014
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12356
Subject(s) - induced pluripotent stem cell , myocyte , hypertrophic cardiomyopathy , phenotype , muscle hypertrophy , embryonic stem cell , biology , stem cell , cell , microbiology and biotechnology , endocrinology , medicine , gene , genetics , biochemistry
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 (hi PSC ) and hi PSC from patients with hypertrophic cardiomyopathy linked to a mutation in the MYBPC 3 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 h ESC ‐ and hi PSC ‐derived cardiomyocytes and their spontaneous contraction rate. Phenylephrine, which normally induces cardiac hypertrophy, had no additional effects under serum conditions. Likewise, hi PSC ‐derived cardiomyocytes from three MYBPC 3 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.