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Durable benefits of cellular postconditioning: Long-term effects of allogeneic cardiosphere-derived cells infused after reperfusion in pigs with acute myocardial infarction
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نویسنده
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kanazawa h. ,tseliou e. ,dawkins j.f. ,de couto g. ,gallet r. ,malliaras k. ,yee k. ,kreke m. ,valle i. ,smith r.r. ,middleton r.c. ,ho c.-s. ,dharmakumar r. ,li d. ,makkar r.r. ,fukuda k. ,marbán l. ,marbán e.
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منبع
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journal of the american heart association - 2016 - دوره : 5 - شماره : 2
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چکیده
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Background--infusion of allogeneic cardiosphere-derived cells (allo-cdcs) postreperfusion elicits cardioprotective cellular postconditioning in pigs with acute myocardial infarction. however,the long-term effects of allo-cdcs have not been assessed. we performed a placebo-controlled pivotal study for long-term evaluation,as well as shorter-term mechanistic studies. methods and results--minipigs underwent 1.5-hour mid-left anterior descending balloon occlusion followed by reperfusion and were randomized to receive intracoronary allo-cdcs or vehicle 30 minutes postreperfusion. left ventriculography (lvg) demonstrated preserved ejection fraction (ef) and attenuation of lv remodeling in cdc-treated pigs. pigs underwent cardiac magnetic resonance imaging (mri) and lvg 1 hour and 8 weeks after therapy to evaluate efficacy. mri showed improvement of ef and attenuation of lv remodeling immediately after allo-cdc infusion. in addition,allo-cdcs improved regional function and decreased hypertrophy 2 months post-treatment. histological analysis revealed increased myocardial salvage index,enhanced vascularity,sustained reductions in infarct size/area at risk and scar transmurality,and attenuation of collagen deposition in the infarct zone of allo-cdctreated pigs at 2 months. allo-cdcs did not evoke lymphohistiocytic infiltration or systemic humoral memory response. short-term experiments designed to probe mechanism revealed antiapoptotic effects of allo-cdcs on cardiomyocytes and increases in cytoprotective macrophages,but no increase in overall inflammatory cell infiltration 2 hours after cell therapy. conclusions--allo-cdc infusion postreperfusion is safe,improves cardiac function,and attenuates scar size and remodeling. the favorable effects persist for at least 2 months after therapy. thus,cellular postconditioning confers not only acute cardioprotection,but also lasting structural and functional benefits. © 2016 the authors.
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کلیدواژه
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Allogeneic transplantation; Cardioprotective effect; Cardiosphere-derived cells
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آدرس
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cedars-sinai heart institute,los angeles,ca,united states,department of cardiology,keio university school of medicine,shinjuku,tokyo, Japan, cedars-sinai heart institute,los angeles,ca, United States, cedars-sinai heart institute,los angeles,ca, United States, cedars-sinai heart institute,los angeles,ca, United States, cedars-sinai heart institute,los angeles,ca, United States, cedars-sinai heart institute,los angeles,ca, United States, cedars-sinai heart institute,los angeles,ca, United States, capricor inc.,los angeles,ca, United States, capricor inc.,los angeles,ca, United States, cedars-sinai heart institute,los angeles,ca,united states,capricor inc.,los angeles,ca, United States, cedars-sinai heart institute,los angeles,ca, United States, gift of life michigan,ann arbor,mi, United States, cedars-sinai biomedical imaging research institute,los angeles,ca, United States, cedars-sinai biomedical imaging research institute,los angeles,ca, United States, cedars-sinai heart institute,los angeles,ca, United States, department of cardiology,keio university school of medicine,shinjuku,tokyo, Japan, cedars-sinai heart institute,los angeles,ca,united states,capricor inc.,los angeles,ca, United States, cedars-sinai heart institute,los angeles,ca, United States
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Authors
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