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Hypothermic Oxygenated Machine Perfusion and Static Cold Storage Drive Distinct Immunomodulation During Liver
Caroline Aspord1,2, Zuzana Macek Jílková1,3, Agnes Bonadona3
1Université Grenoble Alpes, Inserm U 1209, CNRS UMR 5309, Institute for Advanced Biosciences, Grenoble, France.
Transplantation
|March 25, 2025
Summary
Hypothermic oxygenated machine perfusion (HOPE) may reduce immune cell infiltration in liver transplants compared to static cold storage (SCS). This pilot study suggests HOPE dampens innate immune cell entry, guiding future IRI prevention strategies.
Area of Science:
- Transplantation immunology
- Organ preservation techniques
- Ischemia-reperfusion injury (IRI)
Background:
- Organ injury, particularly ischemia/reperfusion injury (IRI), is a significant challenge in liver transplantation.
- Prolonged liver ischemia can impair innate immunity activation.
- Hypothermic oxygenated machine perfusion (HOPE) offers a more physiological approach to liver preservation than static cold storage (SCS), potentially reducing IRI and improving graft quality.
Purpose of the Study:
- To compare the intrahepatic immune responses between HOPE and SCS in liver transplantation.
- To explore the immunological and inflammatory pathways affected by different preservation methods.
Main Methods:
- A pilot study involving 12 liver transplant patients (6 in HOPE group, 6 in SCS group).
- Analysis of liver biopsies using bulk RNA-sequencing and single-cell multiparametric flow cytometry.
- Assessment of immune cell infiltration and function before and after organ storage.
Main Results:
- Significant increases in infiltrated monocytes, conventional type 2 dendritic cells (cDC2s), and neutrophils were observed after SCS, but not HOPE.
- A trend toward reduced immune cell viability was noted after SCS, but not HOPE.
- Distinct functional modulations of intrahepatic immune cells were identified between SCS and HOPE groups.
Conclusions:
- HOPE perfusion appears to dampen the liver infiltration of certain innate immune cells compared to SCS.
- While this pilot study did not definitively conclude on IRI, it provides valuable insights for future research.
- Further studies with larger patient cohorts and later time points are necessary to confirm these findings and develop new IRI prevention strategies.
