Mesenchymal stem cells overexpressing integrin-linked kinase attenuate left ventricular remodeling and improve cardiac function after myocardial infarction

Abstract

In the present study, we investigated whether mesenchymal stem cells (MSCs) overexpressing integrin-linked kinase (ILK) might regulate ventricular remodeling and cardiac function in a porcine myocardial infarction model. ILK-modified MSCs (ILK-MSCs) (n = 8), MSCs (n = 8) or placebo (n = 8) were injected into peri-infarct myocardium 7 days after ligation of the left anterior descending coronary artery. ILK expression was confirmed by immunofluorescence, real-time PCR, Western blot analysis, and flow cytometry. In vitro assays indicated increased proliferation and reduced apoptosis of MSCs due to overexpression of ILK. Echocardiographic, single-photon emission computed tomography and positron emission tomography analyses demonstrated preserved cardiac function and myocardial perfusion. Reduced fibrosis, increased cardiomyocyte proliferation, and enhanced angiogenesis were observed in the ILK-MSC group. Reduced apoptosis, as demonstrated by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling analysis, was also noted. In conclusion, ILK promotes MSC proliferation and suppresses apoptosis. ILK-MSC transplantation improves ventricular remodeling and cardiac function in pigs after MI. It is associated with increased angiogenesis, reduced apoptosis, and increased cardiomyocyte proliferation. This may represent a new approach to the treatment of post-infarct remodeling and subsequent heart failure.

Combination of retinoic acid, dimethyl sulfoxide and 5-azacytidine promotes cardiac differentiation of human fetal liver-derived mesenchymal stem cells

“…In addition, MSCs can produce growth factors and cytokines, and have immunomodulatory capabilities which mainly demonstrated in the field of bone marrow graft-verse-host disease (Ohishi and Schipani 2010;Fujino et al 2014). Therefore, MSCs are considered an ideal seed cells for tissue engineering and regenerative medicine and a promising therapeutic tool for many diseases including heart failure, kidney injury, and myasthenia gravis (Chen et al 2011;Mao et al 2014).…”

Integrins and integrin-related proteins in cardiac fibrosis

“…At the 4-week follow-up study, ILK treated animals showed improved cardiac function, along with decreased: a) infarct size, b) interstitial fibrosis and c) CM apoptosis, as compared to the control group [59, 60]. Additionally, ILK- overexpression in mesenchymal stem cells injected into porcine peri-infarct myocardium 7 days post-MI, preserved cardiac function and myocardial perfusion, reduced fibrosis, increased CM proliferation, and enhanced angiogenesis [61]. These studies suggest ILK overexpression may preserve cardiac function and reduce cardiac fibrosis post-MI.…”

Stem Cell Therapy in Heart Diseases – Cell Types, Mechanisms and Improvement Strategies

“…Moreover, overexpression of anti-apoptotic factors like Bcl-xL and Bcl-2 was found to positively influence the viability and therapeutic efficiency of applied SCs [491,492]. Likewise, overexpression of Akt and integrin-linked kinase (ILK) promoted SC survival in the ischemic myocardium and increased regenerative SC properties [493][494][495][496][497]. Enhanced survival of MSCs was found after co-overexpression of Akt and Ang-1 [498].…”