Inventory of Artificial Liver Support based on the mixed culture system of Hepatocytes with Ito cells

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Cell- cell interactions are important in embryogenesis, in adult physiology and pathophysiology of many disease processes. Co-cultivation of parenchymal and mesenchymal cells has been widely utilized as a paradigm for the study of cell-cell interactions in vitro. In addition, co-cultures of two cell types provide highly functional tissue constructs for use in therapeutic or investigational applications. In this study, we utilize micro fabrication techniques to localize both cell populations in patterned configulations on rigid substrates. We were able to control the level of homotypic interaction in cultures of single cell type and the degree of heterotypic contact in co-culture over a wide range. We have experimentally shown that stellate cells numbers and increased heterotipic cell-cell interactions influences hepatocellular functions. Organs are composed of many individual cell types and together responsible for orchestrating tissue functions. We could mimic liver function in vitro … More and utilize this sytem to elucidate fundamental factors of liver development. We monitored liver -specific functions by urea synthesis and albumin secretion, varied 2-fold with increasing heterotipic cell-cell interactions. Urea is a marker of metabolic function and albumin secretion is a marker of synthetic function. We also investigated lipid metabolism and P450 enzymatic detoxification activity. All data indicated that increasing heterotipic cell-cell interactions contributed maintaining liver specific functions. Moreover we could induced some hepatocyte specific protein expression in ES cells when we co-cultivate ES cells in this system. These evidence indicate that this approach will allow further elucidation of the complex interplay betweentwo cell types as they form a functional model tissue in vitro or as they interact in vivo to form functional organ. Although further investigations are necessary to develop artificial liver for clinical use, this study has clearly shown that appropriate co-clutivation method is numers of advantage over the other approaches. Less