This application requests continued support for the Non-Parenchymal Liver Cell Core established in 2001 by the NIAAA R24 mechanism. The Core provides to local and national alcohol research communities, unique and specialized services of isolation of three non-parenchymal liver cell types (hepatic stellate cells, HSC;Kupffer cells, KG;sinusoidal endothelial cells, SEC) from rodents. The Core's primary mission is to promote cutting-edge, cell-type specific research on alcoholic liver disease (ALD) by enabling direct analysis of the three non-parenchymal liver cell types that actively participate in the pathogenesis of ALD. The Core is integrated into the existing infrastructure of NIAAA-funded Research Center for Alcoholic Liver and Pancreatic Diseases to maximize cross-interactive usage of this Core and the Center's Animal Core and Morphology Core. These cross-utilization approaches result in coordinated support to allow isolation of the cells from the intragastric ethanol infusion models of ALD produced by the Animal Core and parallel and complementary examination of liver tissues and isolated cells by morphological (light and electron microscopic) and immunohistochemical analyses performed by the Morphology Core. For the past 4 years, the Core served 16 Center members and 10 investigators from other institutions, and performed 1665 isolation/preparations: an average of 416 preparations per year. The Core supported 7 of the Center's pilot projects of which 4 were subsequently converted to R01 grants. Total 11 new R01 grants have been acquired with the Core's support, of which 4 grants are obtained by 3 off-site investigators. Total 25 peer-review papers are published or accepted for publication for studies that were supported by the Core. The Core has begun providing services for isolation of HSC and KC from mice, the techniques that are essential for genetic approaches with the use of knockout or transgenic mice. These new services have already been implemented to support 5 investigators. The Core also plans to expand a service of sharing the cells isolated from the intragastric ALD model with center members and alcohol investigators across the nation. The Core is committed to a continued pursuit to circumvent a major limiting factor in research on non-parenchymal liver cell biology in ALD, technical difficulties in cell isolation, to advance the understanding of the cellular basis for the ALD pathogenesis and to help formulate cell-type specific therapeutic framework for the disease.
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