Cardiac drug potential: exploring individual and combined cardiac drugs to promote differentiation of adipose-derived stem cells into cardiomyocytes

Stem cell–based cardiac regenerative medicine holds significant promise for regenerating damaged cardiomyocyte by cardiomyocyte differentiation. Among stem cell types, adipose-derived stem cells (ADSCs) are the most extensively studied due to their ease of isolation and expansion, yet current differentiation protocols remain inefficient and poorly reproducible. Given the well-established roles of certain cardiac drugs—such as Salbutamol, Ivabradine, and Entresto—their potential influence on the regulation of cardiomyocyte differentiation may provide a valuable foundation for advancing differentiation protocols. This study investigates the potential of clinically approved cardiac drugs to enhance ADSC differentiation into cardiomyocytes. ADSCs were isolated from adipose tissue after liposuction surgery from healthy female patients (n = 6, age 23–40 year) using enzymatic methods. ADSCs at early passages (2–3) were treated with Salbutamol, Ivabradine, or Entresto for 21 days. Subsequently, RT-PCR was performed for pluripotency markers (OCT4, NANOG, and SOX2) and cardiac-specific genes (GATA4, NKX2.5, cTNNI, α-MHC). Treatment of ADSCs with each cardiac drug independently led to downregulation of pluripotency-markers compared to controls which indicate a loss of stemness. This was accompanied by increased expression of some early cardiomyocyte markers and slight increase in late cardiomyocyte markers expression, indicating commitment toward cardiac lineage commitment. In light of these results, a combination of these drugs have improved the differentiation of ADSCs into cardiomyocytes and significantly increase gene expression of early cardiomyocyte markers and late cardiomyocyte markers. Clinically approved cardiac drugs promote ADSC differentiation toward the cardiomyocyte lineage, offering a novel and safe approach for cardiac regenerative medicine.