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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
- Source :
- Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
- Publication Year :
- 2016
-
Abstract
- Background Infusion of allogeneic cardiosphere‐derived cells (allo‐ CDC s) postreperfusion elicits cardioprotective cellular postconditioning in pigs with acute myocardial infarction. However, the long‐term effects of allo‐ CDC s 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‐ CDC s 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‐ CDC s 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‐ CDC ‐treated pigs at 2 months. Allo‐ CDC s did not evoke lymphohistiocytic infiltration or systemic humoral memory response. Short‐term experiments designed to probe mechanism revealed antiapoptotic effects of allo‐ CDC s 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.
- Subjects :
- 0301 basic medicine
medicine.medical_specialty
Allogeneic transplantation
Time Factors
Translational Studies
Swine
Biopsy
Myocardial Reperfusion Injury
Myocardial Infarction
Apoptosis
Myocardial Reperfusion
cardiosphere‐derived cells
030204 cardiovascular system & hematology
Ventricular Function, Left
03 medical and health sciences
0302 clinical medicine
Catheter-Based Coronary and Valvular Interventions
Internal medicine
medicine
Animals
Transplantation, Homologous
Coronary Heart Disease
Myocytes, Cardiac
Myocardial infarction
Ventricular remodeling
cardioprotective effect
Cells, Cultured
Original Research
Myocardial reperfusion
Ventricular Remodeling
business.industry
Macrophages
Myocardium
Cell Therapy
Stroke Volume
Stroke volume
medicine.disease
Magnetic Resonance Imaging
allogeneic transplantation
Disease Models, Animal
030104 developmental biology
Cardiology
Swine, Miniature
Cardiology and Cardiovascular Medicine
business
Subjects
Details
- ISSN :
- 20479980
- Volume :
- 5
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Journal of the American Heart Association
- Accession number :
- edsair.doi.dedup.....70dfe58da1d7e25d707fc445e6ebcabb