Hypothermic perfusion of donor heart with a preservation solution supplemented by mesenchymal stem cells

Sevil Korkmaz-Icöz; Shiliang Li; Regina Hüttner; Mihály Ruppert; Tamás Radovits; Sivakkanan Loganathan; Alex Ali Sayour; Paige Brlecic; Felix Lasitschka; Matthias Karck; Gábor Szabó

doi:10.1016/j.healun.2018.12.003

Hypothermic perfusion of donor heart with a preservation solution supplemented by mesenchymal stem cells

J Heart Lung Transplant. 2019 Mar;38(3):315-326. doi: 10.1016/j.healun.2018.12.003. Epub 2018 Dec 6.

Affiliations

¹ Department of Cardiac Surgery, Heidelberg University Hospital, Heidelberg, Germany. Electronic address: korkmaz_sevil@hotmail.com.
² Department of Cardiac Surgery, Heidelberg University Hospital, Heidelberg, Germany.
³ Heart and Vascular Center, Semmelweis University, Budapest, Hungary.
⁴ Department of Cardiac Surgery, Heidelberg University Hospital, Heidelberg, Germany; Department of Anesthesiology, Ruhr University Bochum, St. Josef- and St. Elisabeth Hospital, Bochum, Germany.
⁵ Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.

PMID: 30638838
DOI: 10.1016/j.healun.2018.12.003

Abstract

Background: 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.

Methods: 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 hours with oxygenated, 4°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 hours after transplantation and the myocardial expression of 120 genes using polymerase chain reaction arrays.

Results: Systolic contractility and relaxation parameters were significantly reduced in 15-month-old rats compared with the young rats. After transplantation, systolic function (dP/dt_max: 1,197 ± 94 vs 1,825 ± 279 mm Hg/s at 140 µl; p < 0.05) and diastolic function (dP/dt_min: 737 ± 168 vs 1,200 ± 166 mm Hg/s at 140 µl, 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 anti-oxidant gene superoxide dismutase-2 was up-regulated in the CM-treated grafts compared with the control group grafts.

Conclusions: Perfusion of donor hearts with CM protects against myocardial IRI in 15-month-old rats.

Keywords: 15-month-old rats; cardioprotection; conditioned medium; heart transplantation; mesenchymal stem cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Age Factors
Aged
Animals
Coronary Vessels
Culture Media, Conditioned
Female
Heart Failure / surgery*
Heart Transplantation* / methods
Humans
Male
Mesenchymal Stem Cells*
Middle Aged
Organ Preservation / methods*
Organ Preservation Solutions / administration & dosage*
Perfusion / methods*
Prospective Studies
Rats
Reperfusion Injury / prevention & control*
Time Factors

Substances

Culture Media, Conditioned
Organ Preservation Solutions