Multi-Organ toxicity demonstration in a functional human in vitro system composed of four organs

Carlota Oleaga, Catia Bernabini, Alec S T Smith, Balaji Srinivasan, Max Jackson, William McLamb, Vivien Platt, Richard Bridges, Yunqing Cai, Navaneetha Santhanam, Bonnie Berry, Sarah Najjar, Nesar Akanda, Xiufang Guo, Candace Martin, Gail Ekman, Mandy B. Esch, Jessica Langer, Gladys Ouedraogo, Jose CotovioLionel Breton, Michael L. Shuler, James J. Hickman

Research output: Contribution to journalArticle

148 Scopus citations

Abstract

We report on a functional human model to evaluate multi-organ toxicity in a 4-organ system under continuous flow conditions in a serum-free defined medium utilizing a pumpless platform for 14 days. Computer simulations of the platform established flow rates and resultant shear stress within accepted ranges. Viability of the system was demonstrated for 14 days as well as functional activity of cardiac, muscle, neuronal and liver modules. The pharmacological relevance of the integrated modules were evaluated for their response at 7 days to 5 drugs with known side effects after a 48 hour drug treatment regime. The results of all drug treatments were in general agreement with published toxicity results from human and animal data. The presented phenotypic culture model exhibits a multi-organ toxicity response, representing the next generation of in vitro systems, and constitutes a step towards an in vitro â œ human-on-a-chipâ assay for systemic toxicity screening.

Original languageEnglish (US)
Article number20030
JournalScientific Reports
Volume6
DOIs
StatePublished - Feb 3 2016
Externally publishedYes

ASJC Scopus subject areas

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    Oleaga, C., Bernabini, C., Smith, A. S. T., Srinivasan, B., Jackson, M., McLamb, W., Platt, V., Bridges, R., Cai, Y., Santhanam, N., Berry, B., Najjar, S., Akanda, N., Guo, X., Martin, C., Ekman, G., Esch, M. B., Langer, J., Ouedraogo, G., ... Hickman, J. J. (2016). Multi-Organ toxicity demonstration in a functional human in vitro system composed of four organs. Scientific Reports, 6, [20030]. https://doi.org/10.1038/srep20030