After the storm: an objective appraisal of the efficacy of c-kit+ cardiac progenitor cells in preclinical models of heart disease

Abstract

The falsification of data related to c-kit+ cardiac progenitor cells (CPCs) by a Harvard laboratory has been a veritable tragedy. Does this fraud mean that CPCs are not beneficial in models of ischemic cardiomyopathy? At least 50 studies from 26 laboratories independent of the Harvard group have reported beneficial effects of CPCs in mice, rats, pigs, and cats. The mechanism of action remains unclear. Our group has shown that CPCs do not engraft in the diseased heart, do not differentiate into new cardiac myocytes, do not regenerate dead myocardium, and thus work via paracrine mechanisms. A casualty of the misconduct at Harvard has been the SCIPIO trial, a collaboration between the Harvard group and the group in Louisville. The retraction of the SCIPIO paper was caused exclusively by issues with data generated at Harvard, not those generated in Louisville. In the retraction notice, the Lancet editors stated: “Although we do not have any reservations about the clinical work in Louisville that used the preparations from Anversa's laboratory in good faith, the lack of reliability regarding the laboratory work at Harvard means that we are now retracting this paper”. We must be careful not to dismiss all work on CPCs because of one laboratory’s misconduct. An unbiased review of the literature supports the therapeutic potential of CPCs for heart failure at the preclinical level.