Progressive contractile dysfunction of viable myocardium that surrounds a large infarct leads to
heart failure following acute myocardial infarction (AMI). Experimental evidence indicates that
cellular transplantation may improve the left ventricular (LV) contractile performance, even though
the underlying mechanisms remain undefined. Here, we compared the effect of transplantation of
murine multipotent adult progenitor cells (MAPCs), a population of adult bone marrow-derived
cells that differentiate into cells of mesodermal, endodermal and ectodermal origin, with murine
bone marrow cells (BMCs) or fibroblasts on post-infarct cardiac function by peri-infarct injection
after coronary artery ligation in mice. We demonstrate that, in contrast to the other cell populations,
transplantation of MAPCs significantly improved LV contractile function for at least 8 weeks posttransplantation
and, although BMCs reduced infarct size, the decrease in scar size was substantially
greater in MAPC-treated hearts. As neither MAPCs nor BMCs were present beyond 1 week, the
beneficial effect was not due to differentiation and direct contribution of MAPCs to the vascular
or cardiomyocyte compartment. Significantly more inflammatory cells were present in MAPC- than
BMC-treated hearts at 1 week, which was accompanied by increased vascularity 8 weeks posttransplantation.
We hypothesize that MAPCs indirectly contributed to these effects, by secreting
inflammatory [monocyte chemoattractant protein-1 (MCP)-1], and vascular growth factors [vascular
endothelial growth factor (VEGF), platelet-derived growth factor (PDGF)-BB, and transforming
growth factor (TGF)β1), and others, resulting in increased angiogenensis and cardioprotection