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In a recent commentary, Molkentin and Houser1 have focused on our article in Cell documenting the essential role of endogenous c-kitpos cardiac resident stem/progenitor cells (eCSCs) in myocardial regeneration.2 Their thorough review raised several issues that require our comment. We attempted to address these issues in the same format/space used by the authors but the Editors overruled us. We do not intend to defend our findings against the authors’ or others’ interpretation. Opinions and interpretations are free for everybody but facts are the basis of science and should be challenged with factual evidence. Our goal here is to clarify some overlooked/misinterpreted key factual aspects of our findings, which have significant relevance to the field of regenerative cardiovascular medicine.By producing diffuse myocardial damage in several rodent and genetic fate-mapping murine models in combination with cell transplantation we have shown the following: (1) eCSCs regenerate the cardiomyocytes lost by the primary insult; (2) if the eCSCs are ablated, myocardial regeneration is stunted causing heart failure unless the eCSCs are replaced by exogenous CSCs; (3) Selective suicide of these exogenous replacement CSCs and their progeny abolishes regeneration and severely impairs ventricular performance; (4) the transplanted CSCs can be recovered from the recipient retaining their original characteristics and regenerative potential in vitro/in vivo. Therefore, these data fulfill all proverbial Koch’s postulates3 for CSCs as the cell-type necessary and sufficient for myocardial repair and regeneration.These conclusions rest mainly on 2 experimental facts specifically reviewed by Molkentin and Houser: the use of the isoproterenol (ISO) model of myocardial injury and the in situ labeling and genetic fate tracking of c-kitposeCSCs.We respectfully disagree with the authors’ statement that ISO myocardial damage does not resemble any significant human cardiac disease. Human stress/apical ballooning cardiomyopathy (Takotsubo cardiomyopathy) accounts for up …

Adult c-kit pos Cardiac Stem Cells Fulfill Koch’s Postulates as Causal Agents for Cardiac Regeneration

Adult c-kit ^pos Cardiac Stem Cells Fulfill Koch’s Postulates as Causal Agents for Cardiac Regeneration