Advancements in techniques for human iPSC-derived cardiomyocytes maturation: mechanical and electrical stimulation approaches

Abstract

The maturation of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) is pivotal for their potent application in regenerative medicine, drug screening, and disease modeling. While the emergence of hiPSC-CMs solved the inadequacy of cardiomyocytes in cardiovascular research, they frequently remain immature: more closely resembling fetal rather than adult cardiomyocytes. This immaturity limits their functional utility in both laboratorial and clinical practices. Early methods focused on optimizing culture media with hormones and growth factors to regulate gene transcription related to structural proteins and metabolic enzymes. Subsequently, mechanical training platforms such as static and cyclic stretching were developed to enhance sarcomere alignment and protein expression. Electrical pacing has also been implemented as a crucial method to improve electrophysiological properties by synchronizing contractions and enhancing ion channel expression. The integration of these techniques, along with gene editing and co-culture systems, has significantly advanced the maturation process of hiPSC-CMs. Our review comprehensively explores the advancements in mechanical and electrical stimulation techniques for promoting the maturation of hiPSC-CMs and provides valuable insights for developing effective maturation protocols.

Keywords: Cardiomyocyte maturation; Cardiovascular disease; Electrical pacing; Human-induced pluripotent stem cells; Mechanical stimulation; Tissue engineering.