Stem cell therapy may facilitate cardiac repair after ischemic injury but the optimal cell type and mechanism remain uncertain. This randomized, investigator-blinded, placebo-controlled study compares myocardial angiogenic environment and vascular density after intramyocardial injections of bone-marrow mononuclear (BMNC) or mesenchymal stem cells (MSC) in a canine model of chronic myocardial infarction.

Eleven weeks after coronary ligation, 24 dogs received BMNC, MSC or placebo. They were sacrificed 17 weeks after treatment. Vasular density was studied by immunohistochemistry. Cardiac relative mRNA expression of vascular endothelial growth factor, angiopoietins, fibroblast growth factors (FGF-1 and FGF-2), stromal cell-derived factor 1 (SDF-1) and their receptors (VEGFR-1, VEGFR-2, TEK, FGFR-1 and FGFR-2) was analysed by real time quantitative-PCR in infarcted, border and remote zones.

A higher density of vessels over 20 mm was observed in the infarct tissue after BMNC transfer. FGF-1, FGF-2 and FGFR-1 expression levels decreased with both BMNC and MSC therapies. VEGFR-2 was upregulated in the border zone of the BMNC group while TEK tended to be overexpressed (p=0.075). SDF-1 message levels were higher in the remote region and tended to be higher (p=0.072) in the border zone of the BMNC group compared to MSC. The other factors remained unchanged. TEK message level was inversely related to the wall motion score measured at echocardiography. SDF-1 levels correlated with both VEGFR-2 and TEK. In the canine model of chronic myocardial infarction, functional improvement after BMNC therapy is associated with increased vascular density and upregulation of the pro-angiogenic factors VEGFR-2, TEK and SDF-1 compared to placebo or MSC transfer.