Integrating cell sheets for kidney-on-a-chip applications
June 5-9, 2017
A drug being developed undergoes many stages of development to get to market. Information of the drugs absorption, distribution, excretion, metabolism, and systemic toxicology both short and long term are mandatory by regulatory agencies during clinical trials . Drug-induced organ toxicity leads to 30% of all drugs failing to reach the market. Specifically, nephrotoxicity leads to 19% of all failures during phase III trials but only 2% during preclinical development stages. Current early stage tests for toxicity are widely perceived to be inadequate. 2D cell culture models can produce valuable data for drug discovery but do not accurately predict toxicity. A typical animal study to assess nephrotoxicity uses > 26 rodents, with substantially more animals if both sexes are required. An in vitro model that replaces or reduces animal use in toxicity testing is required for ethical reasons and to reduce species-specific effects. A drug can take 8-12 years and 0.8-1.2 billion US$ to get to market, hence there is a need for a more complex, human cell derived, in vitro model to accurately predict drug toxicity and reduce failure rates during the pre-clinical to clinical transition in drug development.
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William Loewenhardt, Sahithi Kuravi, Rachel E. Saunders, Rachel Lennon, and Brian Derby, "Integrating cell sheets for kidney-on-a-chip applications" in "Biofabrication for Hierarchical in Vitro Tissue Models", Jürgen Groll (University of Würzburg, Germany) Jos Malda (University Medical Centre Utrecht, The Netherlands) Eds, ECI Symposium Series, (2017). http://dc.engconfintl.org/biofab_tissue_model/26
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