Mesenchymal Stem Cell Secretions Improve Donor Heart Function Following Ex-vivo Cold Storage

Abstract Objectives Heart transplantation is the gold standard of treatments for end-stage heart failure, but its use is limited by extreme shortage of donor organs. The time “window” between procurement and transplantation sets the stage for myocardial ischemia/reperfusion injury (I/R), which constrains the maximal storage time and lowers utilization of donor organs. Given mesenchymal stem cell (MSC)-derived paracrine protection, we aimed to evaluate the efficacy of MSC-conditioned medium (MSC-CM) and extracellular vesicles (MSC-EVs) when added to ex-vivo preservation solution on ameliorating I/R-induced myocardial damage in donor hearts. Methods Mouse donor hearts were stored at 0-4°C of Results 6hr-cold ischemia significantly impaired myocardial function, increased cell death, and reduced miR-199a-3p in implanted hearts vs. Conclusions MSC-CM and MSC-EVs confer improved myocardial preservation in donor hearts during prolonged cold static storage and MSC-EVs can be used for intercellular transport of miRNAs in heart transplantation.