Effective derivation of ventricular cardiomyocytes from hPSCs using ascorbic acid-containing maturation medium

Anim Cells Syst (Seoul). 2023 Mar 24;27(1):82-92. doi: 10.1080/19768354.2023.2189932. eCollection 2023.

Abstract

Cardiomyocytes derived from human pluripotent stem cells (hPSCs) can be used in various applications including disease modeling, drug safety screening, and novel cell-based cardiac therapies. Here, we report an optimized selection and maturation method to induce maturation of cardiomyocytes into a specific subtype after differentiation driven by the regulation of Wnt signaling. The medium used to optimize selection and maturation was in a glucose starvation conditions, supplemented with either a nutrition complex or ascorbic acid. Following optimized selection and maturation, more cardiac Troponin T (cTnT)-positive cardiomyocytes were detected using albumin and ascorbic acid than B27. In addition, ascorbic acid enriched maturation of ventricular cardiomyocytes. We compared cardiomyocyte-specific gene expression patterns under different selection and maturation conditions by next-generation sequencing (NGS) analysis. Our optimized conditions will enable simple and efficient maturation and specification of the desired cardiomyocyte subtype, facilitating both biomedical research and clinical applications.

Keywords: Cardiomyocyte; Wnt signaling; albumin; ascorbic acid.

Grants and funding

This research was funded by the Ministry of Trade, Industry and Energy (20009748) and the Korea Institute of Toxicology, Republic of Korea (1711159826), the National Research Foundation of Korea (NRF) grant funded by the Korea Government (MSIT) (NO. 2018R1D1A1B07045689) and Korea Environment Industry and Technology Institute (KEITI) through the Environment Health Action Program, funded by Korea Ministry of Environment (MOE) (2018001360003).