János Bolyai Research Scholarship of the Hungarian Academy of Sciences
(NVKP-16-1-2016-0017)
Heart transplantation is the definitive treatment for end-stage heart failure. A shortage
of donor hearts forced transplant programs to accept older donors and longer ischemic
times. Previous studies have suggested that administration of mesenchymal stem cells
(MSCs) or their conditioned medium (CM) protects the heart against ischemia/reperfusion
injury (IRI). We hypothesized that the preservation of donor hearts with a CM would
protect the graft from IRI after prolonged storage in 15-month-old rats and investigated
mRNA changes attributable to CM. Rat MSCs were isolated and cultured. The CM was used
and characterized by a 90-antibody array, revealing the presence of 28 factors involved
in apoptosis, inflammation, and oxidative stress. Hearts from 15-month-old donor rats
were explanted and continuously perfused for 5 h with oxygenated, 4 degrees C cardioplegic
solution, and supplemented with either regular cell culture medium (control group)
or CM. The hearts were then heterotopically transplanted. We evaluated in-vivo left
ventricular graft function 1.5 h after transplantation and the myocardial expression
of 120 genes using polymerase chain reaction arrays. Systolic contractility and relaxation
parameters were significantly reduced in 15-month-old rats compared with the young
rats. After transplantation, systolic function (dP/dtmax: 1197 +/- 94 vs 1825 +/-
279 mmHg/s at 140 mu l; p < 0.05) and diastolic function (dP/dtmin: 737 +/- 168 vs
1200 +/- 166 mmHg/s at 140 mu l, p < 0.05) were significantly improved in the CM group
compared with controls. Among the genes surveyed, the expressions of 66 were altered.
Genes of pro-inflammatory cytokines and interleukins were down-regulated, whereas
expression of the antioxidant gene superoxide dismutase-2 was up-regulated in the
CM-treated grafts compared with the control group grafts. Perfusion of donor hearts
with CM protects against myocardial IRI in 15-month-old rats.
