To Seek the Holy Grail of Cardiac Progenitor Cells
An Opera in Four Acts
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Discoveries in cardiovascular stem cell biology, myocyte regeneration, and cell transplantation have enormous clinical potentials, yet the field is embroiled in amusing controversies.1–3 The existence of cardiac myocyte progenitor cells (CPCs) in the adult heart, let alone the identity of the genuine CPCs, has been debated and so has the relevance of the primary candidate, namely the resident cardiac progenitor cells expressing the KIT antigen (KITpos cells), to cardiac myocyte generation.1,2,4 Similarly, the choice of the cells, delivery approach, and efficacy of cell transplantation in improving cardiovascular outcomes have remained unsettled as has been the elusive nature of the paracrine factors that are presumably responsible for the improvement in cardiac function post-cell transplantation. Consequently, given these ambiguities, basic and clinical investigators are in the quest to seek the holy grail of CPCs; cells that possess genuine capacities to survive, thrive, differentiate to working myocytes, properly couple with the neighboring resident myocytes; electrically and mechanically, enhance cardiac function, and improve the clinical outcomes, without causing serious adverse events. Similarly, there is an intense focus on defining the responsible mechanisms and identifying and characterizing the elusive paracrine factors.
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Tale of Hippopotamus (Act I)
The Hippo pathway, first discovered in Drosophila and aptly named after hippopotamus because of its key role in determining organ size, is a contact-dependent pathway that regulates cell growth, survival, proliferation, and differentiation.5,6 The pathway comprises a series of upstream molecules that are linked to cell junctions and are sensitive to cell–cell contact. The upstream molecules are also responsive to mechanical properties of cell environment and cell cytoskeleton, particularly actin filament organization. On sensing the stimuli, the upstream Hippo molecules activate a …