Molecular perturbations restrict potential for liver repopulation of hepatocytes isolated from non–heart‐beating donor rats

摘要: Organs from nonheart-beating donors are attractive for use in cell therapy. Understanding the nature of molecular perturbations following reperfusion/reoxygenation will be highly significant donor cells. We studied rats global gene expression with Affymetrix microarrays, hepatic tissue integrity, viability isolated hepatocytes, and engraftment proliferation transplanted cells dipeptidyl peptidase IV-deficient rats. In donors, liver was morphologically intact >24 hours differential 1, 95, or 372 genes, 4, 16 34 after death, respectively, compared heart-beating donors. These differentially-expressed genes constituted prominent groupings ontological pathways oxidative phosphorylation, adherence junctions, glycolysis/gluconeogenesis, as well other discrete pathways. successfully viable hepatocytes especially up to 4 although hepatocyte yield were inferior p<0.05. Similarly, engrafted proliferated transplantation recipient animals, this Gene profiling showed far greater corresponding tissue, including representation focal adhesion, actin cytoskeleton, extracellular matrix-receptor interactions, multiple ligand-receptor signaling insulin, calcium, wnt, Jak-Stat, cascades. Conclusion: Liver remained over prolonged periods death but extensive impaired these Insights into changes offers opportunities improving viability, which advance utility organs therapy applications.