Abstract
Cardiac Progenitor Cells (CPCs) show great potential as a cell resource for restoring cardiac function in patients affected by heart disease or heart failure. CPCs are proliferative and committed to cardiac fate, capable of generating cells of all the cardiac lineages. 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. 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. 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. 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. 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.
Highlights
With morbidity rates associated with cardiovascular diseases in the decline in the developed world from improved treatments and pharmacological intervention, scientists and clinicians have been approaching therapies recently for these diseases with vigor
IPSCs avoid the ethical issues associated with embryonic stem cells (ESCs) and allows for the development of patient-specific derived Cardiac Progenitor Cells (CPCs), which represents an advantage over other cell sources in the creation of immune-compatible cardiac therapies [44,45]
With issues surrounding the safety of induced pluripotent stem cell (iPSC)-based therapies, in terms of the potential risk of tumor formation associated with such therapies or immune rejection of iPS-derived cells from a common donor, scientists are looking at reprogramming from a different perspective [46,47,48]
Summary
With morbidity rates associated with cardiovascular diseases in the decline in the developed world from improved treatments and pharmacological intervention, scientists and clinicians have been approaching therapies recently for these diseases with vigor. CPCs from the heart tissue ( known as putative CPCs) can be isolated and expanded in vitro [27,37,38,39,40] Such cells are hard to access and are present in low numbers in the tissue, making them extremely challenging to harvest and realize their potential [41]. Several studies have identified and isolated multiple CPC populations from distinct stages of cardiac development and heart locations These cells are collectively characterized according to their cell surface and genetic marker expression profiles. The c-KIT receptor binds to the Stem Cell Factor (SCF) which leads to the activation of the signaling pathways Phosphoinositide 3-kinase/Protein Kinase B (PI3K/AKT) and p38 Mitogen-Activated Protein Kinase (MAPK) [54,55] These pathways regulate a variety of CPC functions like self-renewal, proliferation, survival, and migration [54,55,56,57]. C-KIT expression is considered necessary but not sufficient to define CPCs [62]
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