Sca-1+ cardiac progenitor cell therapy with cells overexpressing integrin-linked kinase improves cardiac function after myocardial infarction

Abstract

Background: This study was to investigate the effect of integrin-linked kinase (ILK) on the transplantation efficiency of stem cell antigen-1-positive cardiac progenitor cells (Sca-1 CPCs) in a mouse myocardial infarction (MI) model.

Methods: Sca-1 CPCs were isolated from C57/BL6 mice heart tissues and genetically modified with adenovirus vector containing green fluorescent protein (GFP)/ILK or GFP. Cell viability, migration, DNA synthesis, proliferation, and apoptosis were assessed in vitro. Immediately after MI, treated animals received 5×10 GFP-CPC or ILK-CPC transplantation into the peri-infarct myocardium. Cardiac function, exercise ability, cardiac morphology, angiogenesis, cardiomyocyte apoptosis, as well as ILK-related protein expression were measured. Acute and long-term cell survival after cell transplantation was assessed.

Results: Overexpression of ILK increased the viability, migration, DNA synthesis, proliferation, and survival of Sca-1 CPCs in vitro. Protein expression of phosphorylated Akt and cyclin D1 were up-regulated. In our in vivo experiment, more transplanted cells were found in the peri-infarct myocardium in ILK-CPC group 3 days after cell transplantation, but there was no difference between the two groups 4 weeks later. ILK-CPC group showed reduced infarct size 7 days after cell transplantation. Long-term observation showed improved cardiac function indicated by higher percent fractional shortening and lower left ventricular end systolic diameter/left ventricular end diastolic diameter, better exercise ability, increased angiogenesis, decreased fibrosis and apoptosis, as well as up-regulation of ILK, Cdc42, and Aurora B protein expression in ILK-CPC group 4 weeks after cell transplantation.

Conclusions: ILK-overexpressed Sca-1 CPCs showed improved therapeutic efficacy in MI.