Transcription Factors are the Heart of Heart Regeneration; A Potential Novel Therapeutic Strategy

Myocardial cell injury and following sequelae are the primary reason of death globally. Unfortunately, cardiomyocytes in adults have limited regeneration capacity. Therefore, the generation of neo cardiomyocytes from non-myocardial cells is a surrogate strategy. Transcription factors (TFs) can be recruited to achieve this tremendous goal. Transcriptomic analyses have suggested that GATA, Mef2c, and Tbx5 (GMT cocktail) are master TFs to transdifferentiate/reprogram cell linage of fibroblasts, somatic cells, mesodermal cells into cardiomyocytes. However, adding MESP1, MYOCD, ESRRG, and ZFPM2 TFs induces the generation of more efficient and physiomorphological features for induced cardiomyocytes. Moreover, the same cocktail of transcription factors can induce the proliferation and differentiation of induced/pluripotent stem cells into myocardial cells. The amelioration of impaired myocardial cells involved activation of healing transcription factors, which are induced by inflammation mediators; IL6, tumor growth factor β, and IL22. Transcription factors regulate the cellular and subcellular physiology of cardiomyocytes to include mitotic cell cycling regulation, karyokinesis and cytokinesis, hypertrophic growth, adult sarcomeric contractile protein gene expression, fatty acid metabolism, and mitochondrial biogenesis and maturation. Cell therapy of transcription factors can be applied to cardiogenesis and improve impaired cardiocytes.