Relative roles of CD90 and c-Kit to the regenerative efficacy of cardiosphere-derived cells in humans and in a mouse model of myocardial infarction

Background-the regenerative potential of cardiosphere-derived cells (cdcs) for ischemic heart disease has been demonstrated in mice,rats,pigs,and a recently completed clinical trial (caduceus). cdcs are cd105+ stromal cells of intrinsic cardiac origin,but the antigenic characteristics of the active fraction remain to be defined. cdcs contain a small minority of c-kit+ cells,which have been argued to be cardiac progenitors,and a variable fraction of cd90+ cells whose bioactivity is unclear. methods-we performed a retrospective analysis of data from the caduceus trial and a prospective mouse study to elucidate the roles of c-kit+ and cd90+ cells in human cdcs. here,we show,surprisingly,that c-kit expression has no relationship to cdcs' therapeutic efficacy in humans,and depletion of c-kit+ cells does not undermine the structural and functional benefits of cdcs in a mouse model of myocardial infarction (mi). in contrast,cd90 expression negatively correlates with the therapeutic benefit of cdcs in humans (ie,higher cd90 expression associated with lower efficacy). depletion of cd90+ cells augments the functional potency of cdcs in murine mi. cd90- cdcs secrete lower levels of inflammatory cytokines and can differentiate into cardiomyocytes in vitro and in vivo. conclusion-the majority population of cdcs (cd105+/cd90-/c-kit-) constitutes the active fraction,both in terms of therapeutic efficacy and in the ability to undergo cardiomyogenic differentiation. the c-kit+ fraction is neither necessary for,nor contributory to,the regenerative efficacy of cdcs. © 2014 the authors. published on behalf of the american heart association,inc.,by wiley blackwell.