Insights into Differentiation of Pluripotent Stem Cells to Cardiac Progenitors and Cardiomyocytes

Abstract

The mammalian heart is the first organ formed during development. It forms the crux of the circulatory system of the body and pumps blood (and therefore, nutrients) to all parts of the body. The continuous functioning of the heart is indispensable to the life of the organism. However, such an important organ, that undergoes constant wear and tear, has been shown to have a limited regenerative potential. This, along with a number of genetic, metabolic and environmental factors has resulted in the diseases of the cardiovascular system to become the leading cause of death globally. In spite of decades of research, no effective treatments for cardiovascular diseases especially, ischemic heart diseases, has so far been developed. The conventional strategies are more palliative in nature and do not provide for a long-term solution. On the other hand, the cell-based approaches (mainly adult stem/progenitor cells) that have been developed face limitations in terms of availability of cells having transplantable quality and quantity. Pluripotent stem cells (PSCs) have the ability to self-renew, unlimited proliferative potential and the ability to differentiate to any cell type belonging to the three germ lineages. On account of these properties, PSCs could be used to develop strategies for treatment of ischemic heart diseases. However, the use of PSCs for cell transplantation has limitations in terms of: (a) availability of suitable markers for identification of PSC-derived progenitors or cardiomyocytes, (b) efficient strategies for enrichment of PSC-derived cell types, (c) strategies for scaling up the number of enriched cells and (d) efficient strategies for successful cell transplantation. In our laboratory, we have previously derived and established two transgenic mouse PSC lines, GS-2 embryonic stem cells (ESCs, Singh et al., 2012) and N9 induced pluripotent stem cells (iPSCs, Verma et al., 2017) from the constitutively EGFP-expressing transgenic green GU-2 mouse (Devgan et al., 2003)...