Zonal architecture and microenvironments 523ģ.7. Maintenance of histotypic and phenotypic characteristics 522ģ.3. Considerations for the development of organotypic liver models 519ģ.2. Current challenges for today’s model systems 518ģ. Lessons learned and where we go from here 518Ģ.3. Three-Dimensional spheroid aggregate culture 516Ģ.2. Adhesive and mechanical factors 516Ģ.1.4. Past strategies for maintaining hepatic structure and function in vitro 514Ģ.1.3. The current state of cell-based hepatic culture systems 514Ģ.1. Homotypic hepatocyte interactions 511ġ.3.1.2. Hepatocyte cytoarchitecture and cell polarity 510ġ.3.1.1. Liver sinusoidal endothelial cells 506ġ.3. Basic anatomy and physiology of the liver 503ġ.2.2. In the future, a balanced approach between sample throughput and biological relevance should provide better in vitro tools that are complementary with animal testing and assist in conducting more predictive human risk assessment.ġ.1. As these systems become more widely used for chemical and drug toxicity testing, there will be a corresponding need to establish standardized testing conditions, endpoint analyses and acceptance criteria. This article describes the current and ongoing need for more relevant, organotypic in vitro surrogate systems of human liver and recent efforts to recreate the multicellular architecture and hemodynamic properties of the liver using novel culture platforms. Progress in implementing a more effective strategy for in vitro-in vivo extrapolation and human risk assessment depends on significant advances in tissue culture technology and increasing their level of biological complexity. These systems are less than ideal for longer-term toxicity evaluations and elucidation of key cellular and molecular events involved in primary and secondary adaptation to chemical exposure, or for identification of important mediators of inflammation, proliferation and apoptosis. 2-D static monocultures of primary or immortalized hepatocytes) are limited by their inability to maintain histotypic and phenotypic characteristics over time in culture, including stable expression of clearance and bioactivation pathways, as well as complex adaptive responses to chemical exposure. Generally, conventional in vitro hepatic model systems (i.e. Prediction of chemical-induced hepatotoxicity in humans from in vitro data continues to be a significant challenge for the pharmaceutical and chemical industries.
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