: The Non-Parenchymal Liver Cell Core, now re-named to Integrative Liver Cell Core (ILCC), strives to serve the scientific community of alcoholic liver disease (ALD) and cirrhosis via specialized services of isolation of 6 different lier cell types (hepatocytes, HC; hepatic macrophages, HM; hepatic stellate cells, HSC; liver sinusoidal endothelial cells, LSEC; liver mesothelial cells, MC; and CD133+ liver progenitor cells) from normal rodents and rodent models of ALD and liver fibrosis. To support leading-edge cell type specific research, the ILCC also couples these isolation procedures with the following innovative techniques: 1) Rosa26-reporter-based genetic lineage and cell fate tracing for HC, HSC, and MC in ALD and liver fibrosis; 2) transplantation of monocytes labeled with a fluorescent dye for assessment of transmigration into the liver undergoing alcoholic steatohepatitis (ASH); 3) FACS-based analysis of resident vs. migrating HM to assess their relative contributions to ASH; 4) FACS-based isolation of heterogeneous populations of HSC or vitamin A-depleted HSC from mouse alcoholic liver fibrosis models; and 5) FACS isolation of CD133+ liver progenitors from alcohol-promoted liver cancer and from precancerous alcoholic hepatitis (AH) for investigation on the roles of CD133+ progenitors. To achieve these integrative services, the ILCC effectively collaborates with the Animal Core of the Southern California Research Center for ALPD and Cirrhosis and supports cell type specific analysis including genetic loss or gain of function approaches in rodent models of chronic ASH, AH, alcoholic liver fibrosis, and alcohol-promoted liver cancer. During the current funding cycle, the ILLC has served 31 investigators from 10 institutions by performing 2,204 isolation preparations, supporting 34 publications and acquisition or continuation of 18 NIH grants plus 7 pending applications by a total of 20 investigators. Of these 20 investigators, seven are non-center investigators across the nation, attesting that the ILCC contributes as a national resource. The ILLC has also supported the career development of nine early-career investigators through their cell type-specific research and grant acquisitions (K08, K01, K99R00, three R21s, and two R01s). The proposed ILCC renewal aims to further advance its unique and cutting-edge services of liver cell isolation and analysis and to promote genetic, epigenetic, metabolic, and molecular research on altered cell fate regulation of different liver cell types which manifest as fundamental mechanisms underlying inflammation, fibrosis, and tumorigenesis in ALD.
The proposed renewal of the Integrative Liver Cell Core (ILCC) will promote in-depth research on different liver cell types which are involved in various spectra of liver pathology in alcoholic liver disease (ALD) and liver fibrosis via provision of unique services of isolation and culture of these cells from normal and diseased rodent livers. The ILCC renders these services at the regional and national levels as a NIAAA-supported national resource. The long-term goal of the ILCC is to help scientists develop new therapeutic strategies for ALD and cirrhosis.
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