title: Cyclosporine A-nanoparticles enhance the therapeutic benefit of adipose tissue-derived stem cell transplantation in a swine myocardial infarction model.
abstract: Treatment of myocardial infarction (MI) with adipose-derived stem cells (ASCs) has produced promising results. Cyclosporine A (CsA) inhibits apoptosis by preventing the opening of mitochondrial permeability transition pores. A CsA nanoparticle emulsion (CsA-NP) has lower toxicity and higher efficiency as compared to CsA. In this study, we hypothesized that a combination of ASCs and CsA-NP would enhance the therapeutic efficiency in a swine MI model. MI was induced in pig hearts by occlusion of the left anterior descending artery. The animals that survived MI were divided into four groups and 1 week later received intracoronary ASCs (ASCs, n=6), intracoronary culture media in combination with CsA-NP (CsA-NP, n=6), intracoronary ASCs in combination with CsA-NP (ASCs + CsA-NP, n=6), or remained untreated (control, n=4). Animals were sacrificed 8 weeks later and were evaluated for cardiac function by delayed-enhanced magnetic resonance imaging and immunohistopathology. We observed that the left ventricular ejection fraction (LVEF) was significantly increased in the ASCs + CsA-NP group, compared to the CsA-NP group (53.6%±2.4% versus 48.6%±1.5%, P,0.05), and the ASCs group (53.6%±2.4% versus 48.3%±1.8%, P,0.05). More importantly, the infarct size was significantly smaller in the ASCs + CsA-NP group as compared to the CsA-NP group (6.2±1.7 cm(3) versus 9.1±3.4 cm(3), P,0.05) and the ASCs group (6.2±1.7 cm(3) versus 7.5±0.6 cm(3), P,0.05). These findings were further confirmed by analysis of the expression of cardiomyocyte markers, myosin heavy chain (α-actinin) and troponin T. In addition, the CsA-NP + ASCs treatment promoted neovascularization (P,0.05) and inhibited cardiomyocyte apoptosis (P,0.01) compared to the control group. This study demonstrates that CsA-NP enhanced the therapeutic benefits of ASCs transplantation for MI.
authors.affiliation: Department of Geriatric Cardiology, Chinese General Hospital of the Air Force, Beijing, People's Republic of China.
authors.forename: Qiaoxiang
authors.initials: Q
authors.lastname: Yin
authors.affiliation: Department of Geriatric Cardiology, Beijing Military General Hospital, Beijing, People's Republic of China.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Pei
authors.affiliation: Department of Neurology, Chinese General Hospital of the Air Force, Beijing, People's Republic of China.
authors.forename: Heng
authors.initials: H
authors.lastname: Wang
authors.affiliation: Institute of Geriatric Cardiology, Chinese PLA General Hospital, Beijing, People's Republic of China.
authors.forename: Yusheng
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D017667:Adipocytes / Q000637:transplantation*; D000818:Animals; D003131:Combined Modality Therapy; D016572:Cyclosporine / Q000008:administration & dosage* / Q000737:chemistry; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000737:chemistry; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000628:therapy*; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D033581:Stem Cell Transplantation / Q000379:methods*; D013552:Swine; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D053769:Nanocapsules; D016572:Cyclosporine
keywords: adipose tissue-derived stem cells; cyclosporine A; cyclosporine A nanoparticle emulsion; myocardial infarction