Response to Molkentin’s Letter to The Editor Regarding Article, “The Absence of Evidence Is Not Evidence of Absence: The Pitfalls of Cre Knock-Ins in the c-kit Locus”

Generation of cardiac progenitor cells through epicardial to mesenchymal transition

“…By contrast, c-kit + cells amply contributed to cardiac endothelial cells following MI [51]. Results from these studies gave origin to a debate that is still ongoing [52][53][54][55][56][57].…”

“…On the other end, Nadal-Ginard and Torella replied that in the study by Molkentin's group, experimental controls to verify reliability of the Cre-Lox recombination system in vivo are missing, and thus, their results are uninterpretable [55][56][57].…”

The Quest for the Adult Cardiac Stem Cell

“…Countervailing arguments that have been raised include theoretical concerns that c-kit-Cre knock-in mice were defective for regeneration (because of c-kit haploinsufficiency), or might fail to capture as many c-kit-fated cells in the heart (because of lesser expression than with viral delivery). 88 Rather than emphasize this ensuing technical debate, we wish to emphasize a conceptual difference among the various fate-mapping studies. Even if little or no myocyte creation occurs via a given cell type, under unassisted conditions, we view the relevant translational question as whether myocyte creation by that route can be enhanced, experimentally.…”

Cardiac aging — Getting to the stem of the problem

“…On the contrary, several studies spanning nearly a decade, elegantly demonstrate that c-kit+ CPCs are both necessary and sufficient for cardiac repair and regeneration following injury [8, 56]. Given the ongoing controversies [57–61], the use of CPCs in clinical trials is also being questioned. However, fundamental limitations of the above mentioned studies [54, 55] make it misleading to extrapolate the conclusions to clinical use: A) conclusions drawn from genetically modified mice do not accurately translate into humans.…”