The inability to preserve vascular organs beyond several hours contributes to the scarcity of organs for transplantation. Standard hypothermic preservation at +4 °C (refs. ) limits liver preservation to less than 12 h. Our group previously showed that supercooled ice-free storage at -6 °C can extend viable preservation of rat livers However, scaling supercooling preservation to human organs is intrinsically limited because of volume-dependent stochastic ice formation. Here, we describe an improved supercooling protocol that averts freezing of human livers by minimizing favorable sites of ice nucleation and homogeneous preconditioning with protective agents during machine perfusion. We show that human livers can be stored at -4 °C with supercooling followed by subnormothermic machine perfusion, effectively extending the ex vivo life of the organ by 27 h. We show that viability of livers before and after supercooling is unchanged, and that after supercooling livers can withstand the stress of simulated transplantation by ex vivo normothermic reperfusion with blood.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6776681 | PMC |
http://dx.doi.org/10.1038/s41587-019-0223-y | DOI Listing |
Expert Opin Drug Metab Toxicol
January 2025
Institut de R&D Servier, Paris-Saclay, F-91190 Gif-sur-Yvette, France.
Introduction: Drug-mediated inhibition of bile salt efflux transporters may cause liver injury. In vitro prediction of drug effects toward canalicular and/or sinusoidal efflux of bile salts from human hepatocytes is therefore a major issue, which can be addressed using liver cell-based assays.
Area Covered: This review, based on a thorough literature search in the scientific databases PubMed and Web of Science, provides key information about hepatic transporters implicated in bile salt efflux, the human liver cell models available for investigating functional inhibition of bile salt efflux, the different methodologies used for this purpose, and the modes of expression of the results.
The kinetically-derived maximal dose (KMD) is defined as the maximum external dose at which kinetics are unchanged relative to lower doses, e.g., doses at which kinetic processes are not saturated.
View Article and Find Full Text PDFCell Mol Biol (Noisy-le-grand)
January 2025
Université Joseph KI-ZERBO, Laboratoire de Biologie Moléculaire et de Génétique (LABIOGENE), 03 BP 7021 Ouagadougou 03, Burkina Faso.
Hepatitis B virus (HBV) is a significant cause of liver disease and cancer worldwide. Understanding the genetic factors influencing HBV evolution is crucial for developing effective prevention and treatment strategies. Host genetic and environmental factors particularly influence the evolution of this infection.
View Article and Find Full Text PDFPak J Pharm Sci
January 2025
Department of Pharmacy, the First Affiliated Hospital of Soochow University, Suzhou City, Jiangsu Province, China.
Berberine (BBR), an isoquinoline alkaloid abundant in Coptis chinensis, exhibits anti-tumor and hypoglycemic properties. The regulation of tumor cell homeostasis and metabolism is greatly influenced by Hypoxia-inducible factor-1α (HIF-1α). This research aims to elucidate whether BBR inhibits the progression of hepatocellular carcinoma (HCC) by modulating HIF-1α expression.
View Article and Find Full Text PDFXi Bao Yu Fen Zi Mian Yi Xue Za Zhi
January 2025
Central Laboratory, Chengdu University of TCM, School of Clinical Medicine, Chengdu University of TCM, Chengdu 610072, China.
Efferocytosis refers to the process of phagocytes engulfing and clearing the cells after programmed cell death. In recent years, an increasing number of studies have shown that the mechanisms of efferocytosis are closely related to drug-induced liver injury, hepatic ischemia-reperfusion injury, viral hepatitis, cholestatic liver diseases, metabolic-associated fatty liver disease, alcoholic liver disease, and other liver disorders. This review summarized the research progress on the role of efferocytosis in liver diseases, with the hope of providing new targets for the prevention and treatment of liver diseases.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!