4.2 Article

LIVER TISSUE MODEL FOR DRUG TOXICITY SCREENING

Journal

JOURNAL OF MECHANICS IN MEDICINE AND BIOLOGY
Volume 11, Issue 2, Pages 369-390

Publisher

WORLD SCIENTIFIC PUBL CO PTE LTD
DOI: 10.1142/S0219519411004083

Keywords

Hepatotoxicity; 3D models; in vitro drug screening; nanotechnology

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Understanding the mechanisms involved in the biotransformation of new drugs and their toxicological implications is important for drug development. In this regard, a lot of effort has been put into research to recreate the liver tissue in the laboratory for the purpose of drug screening. This has also helped to minimize the use of laboratory animal and reduce incidence of post-market withdrawal of drugs. Despite the progress made so far, cell source remains a major limitation since primary human hepatocytes are scarce and the various cell alternatives do not express all the genes found in the normal liver. In terms of tissue construct, there is a current shift to 3D models since the cell-cell interactions found in the 3D configuration enhance the morphology and function of hepatocytes. Furthermore, the engineered tissue's performance can be optimized by cocultures, perfusion-based systems, and the use of scaffolds. Nanotechnology seems promising in the field of tissue engineering, as it has been proven that cell-matrix interactions at the nano level can influence greatly on the outcome of the tissue. The review explores the various cell sources, the 3D model, flow-based systems, cocultures, and nanoscaffolds use in hepatocytes in vitro drug testing

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