Open AccessMulti-Organ toxicity demonstration in a functional human in vitro system composed of four organs
Author(s) -
Carlota Oleaga,
Catia Bernabini,
André Smith,
Balaji Srinivasan,
Max Jackson,
William McLamb,
Vivien Platt,
Richard J. Bridges,
Yuanqing Cai,
Navaneetha Santhanam,
Bonnie J. Berry,
Sarah A. Najjar,
Nesar Akanda,
Xiufang Guo,
Candace Martin,
Gail Ekman,
Mandy B. Esch,
Jessica Langer,
Gladys Ouédraogo,
José Cotovio,
Lionel Breton,
Michael L. Shuler,
James J. Hickman
Publication year - 2016
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep20030
Subject(s) - toxicity , in vitro , pharmacology , drug toxicity , drug , organ system , medicine , biology , pathology , biochemistry , disease
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 “human-on-a-chip” assay for systemic toxicity screening.