Human Liver Tissue & Hepatocytes Research Resource (HLTHRR) - PROJECT SUMMARY/ABSTRACT The overall goal of the Human Liver Tissue & Hepatocytes Research Resource (HLTHRR) program is to provide normal human liver tissue and normal human hepatocytes (HC) and non-parenchymal cells (NPC) including NPC sub-fractions (Kupffer cells, sinusoidal endothelial cells, cholangiocytes, and stellate cells) as a core lab to biomedical researchers across the USA. Primary human hepatocytes (HC) continue to be the most relevant cellular resource to model liver functions and advance our knowledge of mechanisms underlying metabolic enzymes, drug discovery, toxicology, viral and alcoholic hepatitis, regeneration capacities, and most importantly human liver diseases. The NIDDK has funded a research program for over 25 years to isolate and distribute primary human hepatocytes (HC) and liver tissues for research purposes to academic scientists who are primarily NIH-funded. The initial program was known as Liver Tissue Cell Distribution System (LTCDS), and more recently (2022-2024) Human HC Isolation and Distribution (HHID) in Dr. Geller's lab at Pitt with NIDDK bridge funding as an administrative supplement to our active P30 DK120531 “Pittsburgh Liver Research Center” (PI-Monga). All human HC isolations have been at the University of Pittsburgh (Pitt) as the core lab in the USA, and cells distributed to PIs throughout the country. In this HLTHRR proposal, Dr. Geller's lab will continue to provide human liver tissues and normal human HC as a core service to NIH-funded investigators throughout the USA. Also, as part of our HLTHRR proposal, NPC from normal human livers will be separated into high-purity fractions of Kupffer cells (KC), liver sinusoidal endothelial cells (LSEC), cholangiocytes, and stellate cells in Dr. Soto-Gutierrez's Pathology lab at Pitt. We will also develop and deploy a website to facilitate all aspects of cell and tissue distribution. This will include PI registration, announcements of tissue and cell availability, submission and tracking of cell requests, confirmation of shipping, quality feedback, annual summary of HLTHRR progress and related publications. The HLTHRR is a unique and extraordinary resource for the biomedical research community to accelerate liver translational research with the potential to hasten breakthrough discoveries.