Donor heart preservation with hypoxic-conditioned medium-derived from bone marrow mesenchymal stem cells improves cardiac function in a heart transplantation model

Abstract Background In heart transplantation, donor hearts inevitably suffer from ischemia/reperfusion (I/R) injury, which leads to primary graft dysfunction and affects patients’ survival rate. Bone marrow mesenchymal stem cells (BMSCs) have been reported attenuate myocardial I/R injury via their paracrine effects, can be enhanced by hypoxic preconditioning. We hypothesized that the preservation with conditioned medium (CdM) derived BMSCs would improve post-transplant function. Methods Normoxic or CdM were isolated rat cultured under normoxic (20% O 2 ) (1% condition. Donor explanted; stored in cardioplegic solution supplemented either a (vehicle), (N-CdM), (H-CdM); then heterotopically transplanted. Antibody arrays performed compare differences between CdM. Results After was associated shorter time return of spontaneous contraction left ventricular systolic diameter, lower histopathological scores, higher ejection fraction, fractional shortening transplanted hearts. The cardioprotective effects may inhibition apoptosis inflammation, as reflected less TUNEL-positive levels plasma proinflammatory cytokines (interleukin-1β, interleukin-6, tumor necrosis factor-α) cardiac troponin I N-CdM group compared vehicle group. These therapeutic further revealed nine proteins significantly increased Furthermore, groups, protein PI3K p-Akt/Akt ratio H-CdM However, no significant difference found phosphorylation Smad2 Smad3 for among three groups. Conclusions Our results indicate solution-enriched novel promising