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Technique of Subnormothermic Ex Vivo Liver Perfusion for the Storage, Assessment, and Repair of Marginal Liver Grafts
Published on: August 13, 2014
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The Distinct Innate Immune Response of Warm Ischemic Injured Livers during Continuous Normothermic Machine Perfusion
Joris Blondeel1,2, Nicholas Gilbo1,2, Veerle Heedfeld1,2
1Department of Abdominal Transplant Surgery and Transplant Coordination, University Hospitals Leuven, 3000 Leuven, Belgium.
International Journal of Molecular Sciences
|August 26, 2023
Summary
Normothermic machine perfusion (NMP) impacts liver immunity differently based on warm ischemia (WI) history. WI livers show a distinct, less inflammatory immune response during NMP and reperfusion, suggesting a reconditioning effect.
Area of Science:
- Transplantation immunology
- Organ preservation research
Background:
- Normothermic machine perfusion (NMP) offers superior liver graft preservation over static cold storage.
- NMP enables viability assessment for high-risk liver grafts.
- The impact of NMP on the liver's innate immune response is not fully understood.
Purpose of the Study:
- To investigate the innate immune response in liver grafts subjected to continuous NMP (cNMP) after direct procurement (DP) versus warm ischemia (WI).
- To compare immune profiles during cNMP and subsequent whole blood (WB) reperfusion between DP and WI liver grafts.
Main Methods:
- Comparison of immune responses in DP (n=5) and WI (n=5) liver grafts during 6-hour cNMP.
- Analysis of perfusate cytokine levels (TNF-α, IL-8, TGF-β, IL-10) and cellular signaling.
- Assessment of transaminase levels, endoplasmic stress, apoptotic signaling, and neutrophil mobilization post-NMP and 12-hour WB reperfusion.
Main Results:
- WI livers had higher transaminases during cNMP but not after WB reperfusion.
- WI livers showed lower TNF-α and higher TGF-β during cNMP and WB reperfusion.
- Increased endoplasmic stress and apoptosis were observed in WI livers during cNMP.
- Neutrophil mobilization was reduced in WI livers at the end of cNMP.
- Livers exhibited blunted cytokine release during WB reperfusion, irrespective of ischemic damage.
Conclusions:
- Warm ischemia induces a distinct innate immune response in liver grafts undergoing NMP.
- NMP shifts the cytokine profile towards an anti-inflammatory phenotype during perfusion and reperfusion.
- Pro-apoptotic signaling is heightened during cNMP in WI livers.
- NMP demonstrates a potential reconditioning effect, evidenced by blunted cytokine release post-reperfusion.
