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Brain-dead donor heart conservation with a preservation solution supplemented by a conditioned medium from mesenchymal stem cells improves graft contractility after transplantation

Hearts are usually procured from brain-dead (BD) donors. However, brain death may induce hemodynamic instability, which may contribute to posttransplant graft dysfunction. We hypothesized that BD-donor heart preservation with a conditioned medium (CM) from mesenchymal stem cells (MSCs) would improve...

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Main Authors: Korkmaz-İçöz, Sevil (Author) , Li, Kunsheng (Author) , Loganathan, Sivakkanan (Author) , Ding, Qingwei (Author) , Ruppert, Mihály (Author) , Radovits, Tamás (Author) , Brlecic, Paige (Author) , Sayour, Alex A (Author) , Karck, Matthias (Author) , Szabó, Gábor (Author)
Format: Article (Journal)
Language:English
Published: 2020
In: American journal of transplantation
Year: 2020, Volume: 20, Issue: 10, Pages: 2847-2856
ISSN:1600-6143
DOI:10.1111/ajt.15843
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1111/ajt.15843
Verlag, kostenfrei, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1111/ajt.15843
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Author Notes:Sevil Korkmaz-Icöz, Kunsheng Li, Sivakkanan Loganathan, Qingwei Ding, Mihály Ruppert, Tamás Radovits, Paige Brlecic, Alex A Sayour, Matthias Karck, Gábor Szabó
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Summary:Hearts are usually procured from brain-dead (BD) donors. However, brain death may induce hemodynamic instability, which may contribute to posttransplant graft dysfunction. We hypothesized that BD-donor heart preservation with a conditioned medium (CM) from mesenchymal stem cells (MSCs) would improve graft function after transplantation. Additionally, we explored the PI3K pathway's potential role. Rat MSCs-derived CM was used for conservation purposes. Donor rats were either exposed to sham operation or brain death by inflation of a subdural balloon-catheter for 5.5 hours. Then, the hearts were explanted, stored in cardioplegic solution-supplemented with either a medium vehicle (BD and sham), CM (BD + CM), or LY294002, an inhibitor of PI3K (BD + CM + LY), and finally transplanted. Systolic performance and relaxation parameters were significantly reduced in BD-donors compared to sham. After transplantation, systolic and diastolic functions were significantly decreased, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)-positive cells and endonuclease G positive cells were increased in the BD-group compared to sham. Preservation of BD-donor hearts with CM resulted in a recovery of systolic graft function (dP/dtmax: BD + CM: 3148 ± 178 vs BD: 2192 ± 94 mm Hg/s at 110 µL, P < .05) and reduced apoptosis. LY294002 partially lowered graft protection afforded by CM in the BD group. Our data suggest that PI3K/Akt pathway is not the primary mechanism of action of CM in improving posttransplant cardiac contractility and preventing caspase-independent apoptosis.
Item Description:First published: 11 March 2020
Gesehen am 10.01.2022
Physical Description:Online Resource
ISSN:1600-6143
DOI:10.1111/ajt.15843

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