Premium
Gene network analysis of liver allografts preserved with machine perfusion (649.10)
Author(s) -
Paranjpe Shirish,
Fontes Paulo,
Vodovotz Yoram,
Michalopoulos George
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.649.10
Subject(s) - perfusion , liver transplantation , andrology , biology , cytokine , transplantation , immunology , medicine
Machine perfusion (MP) with a cell‐free oxygen carrier solution (CFOCS) was compared to cold static preservation (CSP) in a porcine model. Methods: Two groups of 6 animals underwent liver transplantation after 9 hours of cold ischemia time. Clinical and laboratorial data was obtained in additional to serial histological and electron microscopy analysis. Affymetrix gene‐arrays were performed on liver tissues from both groups. A cytokine profile was obtained from liver tissues and perfusate with Luminex. Additional metabolomics analysis (Metabolon) was performed. Results: The MP group had 100% survival and the CSP group had 33% survival. A significant (p<0.004) benefit of MP was detected after 16 different variables were analyzed. Over‐expression of genes associated with general metabolic functions, anti‐inflammatory, regenerative and protective mechanisms against free radicals were observed in the MP group. Genes associated with hepatic system development and cellular proliferation were significantly up‐regulated in the MP group. Genes associated with critical metabolic networks were significantly down regulated in the CSP group compared to MP livers. The lipid metabolic pathway was up regulated in the CSP group. Signaling pathways that are critical for liver growth (NF‐kB, PI3K/AT, ErbB) were significantly up‐regulated in MP liver samples when compared to CSP group. INF‐α, IL‐1β, IL‐1RA, IL‐4, IL‐10, IL‐12p40, IL‐18 and TNF‐α showed significant differences between the groups in liver tissues analyzed during preservation. Ingenuity® pathway analysis of functional groups revealed that genes associated with liver damage were significantly down regulated in the MP group. The CSP group showed significant up‐regulation of genes associated with liver pathology when compared to the MP group. Conclusions: MP with a CFOCS up‐regulated a regenerative and prosurvival response when compared to CSP. Grant Funding Source : NIH GrantNo.CA35373,CA103958 & Rangos Fund for Enhancement of Researchin Pathology.