Objectives This study assessed the potential enhancement therapeutic efficiency of adipose-derived stem cells (ASCs) combination with cyclosporine A nanoparticles emulsion (CsA-NP) in a swine model of myocardial infarction (MI).
Methods MIwas induced in pig hearts by occlusion of the left anterior descending artery (LAD). The swines that survived MI one week later were divided into four groups and received: intracoronary ASCs (ASCs, n = 6); intracoronary culture media combination with CsA-NP (CsA-NP, n = 6); intracoronary ASCs combination with CsA-NP (ASCs + CsA-NP, n = 6); or remained untreated (control,n = 4). Swines were sacrificed 8 weeks later for cardiac function evaluation by delayed-enhanced magnetic resonance imaging (DE-MRI) and for evaluation by immunohistopathology.
Results At 8 weeks’ follow-up, LVEF increased in all groups,significantly increased in CsA-NP + ASCs group than in control group (53.6 ± 2.4,% vs 46.2 ± 3.9,% P < 0.01), CsA-NP group (53.6 ± 2.4,% vs 48.6 ± 1.5,% P < 0.05) and ASCs groups (53.6 ± 2.4,% vs 48.3 ± 1.8,% P < 0.05); In contrast, LVEDV significantly decreased in CsA-NP + ASCs group than in control group (P < 0.05) and CsA-NP group (P < 0.05); A similar trend was measured for LVESV. More importantly, infarct size (cm3) was significantly smaller in CsA-NP + ASCs group compared with control group (6.2 ± 1.7 vs 9.8 ± 2.4, P < 0.01), CsA-NP group (6.2 ± 1.7 vs 9.1 ± 3.4, P < 0.05) and ASCs group (6.2 ± 1.7 vs7.5 ± 0.6, P < 0.05). The number of surviving cells significantly increased (38 ± 7.8 vs 15 ± 8.6 cells/cm2, P < 0.01) and identified expression of the cardiomyocyte specific markers (troponin I and myosin heavy chain) of these ASCs + CsA-NP- treated swines. In the infarct core,vascular density was significantly higher in the CsA-NP + ASCs group than in the ASCs (49 ± 15/mm2 vs 38 ± 14/mm2, P < 0.01) alone group and CsA-NP alone group (49 ± 15/mm2 vs 38.5 ± 13/mm2, P < 0.01). Histological samples also showed that reduce fibrotic tissue, and down-regulation of activation of caspase-3.
Conclusions The present study suggests that CsA-NP further enhance the therapeutic benefits of ASCs transplantation into the infarcted myocardium.
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