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Status |
Public on Apr 10, 2019 |
Title |
Normothermic machine perfusion (NMP) inhibits proinflammatory responses in the liver and promotes regeneration |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
Background and Aims: Liver transplantation is a successful treatment for patients with liver failure. However, organ shortage results in over 11% of patients loosing their chance of a transplant due to worsening of their liver disease. Ischemia/reperfusion injury (IRI) is the major cause leading to graft loss after liver transplantation. Therefore, novel methods of organ-preservation have been developed in recent years to minimize IRI. One such device is the OrganOx metra, a normothermic machine perfusion (NMP) device providing oxygen and nutrition to allow aerobic metabolism and minimizing IRI. OrganOx metra has presented with several advantages compared to conventional cold storage (CS). We aimed to confirm the impact of NMP on reducing IRI and to define the underling mechanisms. Methods: We compared 12 NMP with 27 CS-preserved livers by performing gene microarray, immunoprofiling of hepatic lymphocytes and immunochemistry staining of liver tissues for assessing necrosis, platelet deposition and neutrophil infiltration, and the status of steatosis after NMP or CS pre- and post-reperfusion. Results: Recipients receiving NMP grafts showed significantly lower peak AST levels than those receiving CS grafts. NMP altered gene-expression profiles of liver tissue from pro-inflammation to pro-healing and regeneration. NMP also reduced the number of IFN- and IL-17 producing T cells and enlarged CD4posCD25highCD127negFOXP3pos Treg pool. NMP liver tissues showed less necrosis and apoptosis in the parenchyma and fewer neutrophils and platelet infiltration compared to CS liver tissues. Conclusion: Reduced IRI in NMP recipients was the consequence of the combination of inhibiting inflammation and promoting graft regeneration.
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Overall design |
Gene expression of 15 NMP with 11 preserved livers (CONTROL) under pre- and post-reperfusion.
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Contributor(s) |
Jassem W, Xystrakis E, Ghnewa YG, Lozano JJ, Sanchez A, Ma Y |
Citation(s) |
30561835 |
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Submission date |
Apr 04, 2018 |
Last update date |
Apr 10, 2019 |
Contact name |
Juanjo Lozano |
E-mail(s) |
juanjo.lozano@ciberehd.org
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Organization name |
CIBEREHD
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Department |
Plataforma de Bioinformatica
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Street address |
C/ Rosselló 153
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City |
Barcelona |
ZIP/Postal code |
08036 |
Country |
Spain |
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Platforms (1) |
GPL14951 |
Illumina HumanHT-12 WG-DASL V4.0 R2 expression beadchip |
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Samples (48)
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Relations |
BioProject |
PRJNA448772 |