Cellular Post-Conditioning: Allogeneic Cardiosphere-Derived Cells Reduce Infarct Size and Attenuate Microvascular Obstruction When Administered After Reperfusion in Pigs With Acute Myocardial Infarction

Background— Intracoronary (IC) delivery of cardiosphere-derived cells (CDCs) has been demonstrated to be safe and effective in porcine and human chronic myocardial infarction (MI). However, IC delivery of CDCs after reperfusion in acute MI has never been assessed in a clinically-relevant large animal model. We tested CDCs as adjunctive therapy to reperfusion in a porcine model of MI. Methods and Results— First, escalating doses (5, 7.5 and 10 million [M] cells) of allogeneic CDCs (allo-CDCs) were administered IC 30 minutes after reperfusion. Forty-eight hours later, left ventriculography (LVG) but not 5M CDCs, relative to control. In the pivotal study, IS, MVO, cardiomyocyte apoptosis and adverse LV remodeling were all smaller in the CDC group than in sham or placebo groups. In addition, serum troponin I level at 24 hours was lower after CDC infusion than that in the placebo or sham groups, consistent with the histologically-demonstrated reduction in IS. Conclusions— IC delivery of allo-CDCs is safe, feasible and effective in cardioprotection, reducing IS, preventing MVO and attenuating adverse acute remodeling. This novel cardioprotective effect, which we call “cellular postconditioning”, differs from previous strategies to reduce IS in that it works even when initiated with significant delay after reflow.