![]() However, the application of CPCs has not been straight-forward particularly in chronic infarcts, where CPCs are associated with senescence, decreased telomerase activity and increased apoptosis. Therefore, CPCs present a more effective cell source than cardiomyocytes for cell-based regenerative strategies. In contrast to terminally differentiated cardiomyocytes, CPCs are highly proliferative and can theoretically differentiate into all the necessary cardiac cell types for effective reconstitution of damaged cardiac tissue and promoting its neovascularization. Nevertheless, several studies report the evidence of a progenitor population from resident cardiac stem cells (CSCs) in the heart, called Cardiac Progenitor Cells (CPCs). This puts emphasis on the role of a precursor cell type capable of extensive expansion and differentiation into the key cell players of cardiac regeneration.Įven though some level of cell turnover has been observed in the adult heart, cells with self-renewal or potency capabilities are generally considered lacking in this tissue. Furthermore, other cell types like smooth muscle cells, and endothelial cells can suffer from collateral damage and their functional renewal is vital for effective heart regeneration. This is because cardiomyocytes have very limited proliferative ability and as a result, they are unable to repopulate and replenish the damaged tissue efficiently. However, transplanting cardiomyocytes to repair diseased hearts has shown to yield only transient responses as most cells are eventually lost in the host environment. ![]() Cardiomyocytes are the main cardiac cell type that is lost in cardiovascular disorders, like heart failure, myocardial infarction, and ischemia, and therefore, replacing these cells could potentially restore heart function. This catapulted research towards cell-based therapies for cardiac regeneration. Therefore, the only long-term solution relies on heart transplantation, but this does not come without its own issues such as insufficient number of donors coupled with the requirement for a life-long immunosuppressive therapy. The turnover of cardiomyocytes in the adult heart is around 1% per year which is insufficient to counter the loss caused by MI that can lead to loss of around 1 billion cardiomyocytes. Cardiac regeneration, following injury, is still an unresolved debate over whether it is attributed to dedifferentiation and proliferation of resident cardiomyocytes or from an inherent trigger in differentiation of cardiac stem or progenitor cells in putative cell niches within the heart. The heart was long viewed as a post-mitotic or terminally differentiated organ with no ability to regenerate or repair, a dogma that has been challenged abundantly in recent years. This review highlights recent developments and limitations in the generation and use of CPCs from stem cells, and the trends that influence the direction of research to promote better application of CPCs. ![]() Recent advances in biomaterials to mimic the native cardiac microenvironment have shown promise to influence CPC regenerative functions, while being capable of integrating with host tissue. However, the precise stoichiometry and spatiotemporal activity of these factors and the genetic interplay during embryonic CPC development remain challenging to reproduce in culture, in terms of efficiency, numbers, and translational potential. The iPSCs and direct reprogramming of somatic cells have been attempted to produce CPCs and, in this process, a variety of chemical and/or genetic factors have been evaluated for their ability to generate, expand, and maintain CPCs in vitro. These cells offer a significant shift in paradigm over the use of human induced pluripotent stem cell (iPSC)-derived cardiomyocytes owing to the latter’s inability to recapitulate mature features of a native myocardium, limiting their translational applications. ![]() CPCs are proliferative and committed to cardiac fate, capable of generating cells of all the cardiac lineages. Cardiac Progenitor Cells (CPCs) show great potential as a cell resource for restoring cardiac function in patients affected by heart disease or heart failure. ![]()
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