Acta Academiae Medicinae Sinica

Abstract:

Objective To evaluate the efficacy of cyclosporine A-nanoparticles emulsion(CsA-NP)combined with adipose tissue-derived stem cells(ASCs)transplantation therapy for acute myocardial infarction(AMI)in a miniswine model.Methods CsA-NP emulsion was prepared by the high-pressure homogenization method.Models were performed by coronary angioplasty for percutaneous balloon occlusion of left anterior descending artery(LAD).A total of 17 miniswines survived after AMI were divided into four groups:control group(n=5),CsA-NP group(n=4),ASCs group(n=4),and CsA-NP+ASCs group(n=4).ASCs or saline were delivered by intracoronary injection one week after AMI.Before cell transplantation and 8 weeks after cell transplantation,delayed-enhanced magnetic resonance imaging(DE-MRI)was performed to evaluate cardiac function and viability.The infarcted myocardium and implanted cells were histologically studied.Results Eight weeks after treatment,the left ventricular ejection fraction(LVEF)significantly increased in the CsA-NP+ASCs group when compared with the ASCs group[(53.6±2.4)% vs.(48.3±1.8)%,P<0.05];meanwhile,the infarct size significantly decreased[(6.2±1.7)cm³ vs.(7.5±0.6)cm³,P<0.05]and the thickness of the ventricular wall significantly increased(P＜0.05).Histology showed that the number of surviving cells increased nearly by three times in the CsA-NP+ASCs group,and the expressions of the cardiomyocyte specific markers(cTnT and α-actin)were detected.Histological samples also showed that CsA-NP+ASCs group reduced fibrotic tissue,and down-regulated the activation of Caspase-3.Conclusion The CsA-NP+ASCs combination therapy can enhance the viability of ASCs by improving LVEF and preventing LV expansion,which may be explained that CsA-NP has the anti-apoptotic effect and can promote the survivals and proliferation of ASCs.

Key words: cyclosporine A, nanoparticles, stem cell, adipose, apoptosis, acute myocardial infarction