We hypothesized that mesenchymal stem cells (MSCs) overexpressing insulin-like 
growth factor (IGF)-1 showed improved survival and engraftment in the infarcted 
heart and promoted stem cell recruitment through paracrine release of stromal 
cell-derived factor (SDF)-1alpha. Rat bone marrow-derived MSCs were used as 
nontransduced ((Norm)MSCs) or transduced with adenoviral-null vector 
((Null)MSCs) or vector encoding for IGF-1 ((IGF-1)MSCs). (IGF-1)MSCs secreted 
higher IGF-1 until 12 days of observation (P<0.001 versus (Null)MSCs). Molecular 
studies revealed activation of phosphoinositide 3-kinase, Akt, and Bcl.xL and 
inhibition of glycogen synthase kinase 3beta besides release of SDF-1alpha in 
parallel with IGF-1 expression in (IGF-1)MSCs. For in vivo studies, 70 muL of 
DMEM without cells (group 1) or containing 1.5x10(6) (Null)MSCs (group 2) or 
(IGF-1)MSCs (group 3) were implanted intramyocardially in a female rat model of 
permanent coronary artery occlusion. One week later, immunoblot on rat heart 
tissue (n=4 per group) showed elevated myocardial IGF-1 and phospho-Akt in group 
3 and higher survival of (IGF-1)MSCs (P<0.06 versus (Null)MSCs) (n=6 per group). 
SDF-1alpha was increased in group 3 animal hearts (20-fold versus group 2), with 
massive mobilization and homing of ckit(+), MDR1(+), CD31(+), and CD34(+) cells 
into the infarcted heart. Infarction size was significantly reduced in cell 
transplanted groups compared with the control. Confocal imaging after 
immunostaining for myosin heavy chain, actinin, connexin-43, and von Willebrand 
factor VIII showed extensive angiomyogenesis in the infarcted heart. Indices of 
left ventricular function, including ejection fraction and fractional 
shortening, were improved in group 3 as compared with group 1 (P<0.05). In 
conclusion, the strategy of IGF-1 transgene expression induced massive stem cell 
mobilization via SDF-1alpha signaling and culminated in extensive 
angiomyogenesis in the infarcted heart.