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 Cotovio; Lionel Breton; Michael L. Shuler; James J. Hickman

doi:10.1038/srep20030

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

Department of Biomedical & Chemical Engineering

Research output: Contribution to journal › Article › peer-review

340 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 language	English (US)
Article number	20030
Journal	Scientific reports
Volume	6
DOIs	https://doi.org/10.1038/srep20030
State	Published - Feb 3 2016

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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, Article 20030. https://doi.org/10.1038/srep20030

Oleaga, C, Bernabini, C, Smith, AST, 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, MB, Langer, J, Ouedraogo, G, Cotovio, J, Breton, L, Shuler, ML & Hickman, JJ 2016, 'Multi-Organ toxicity demonstration in a functional human in vitro system composed of four organs', Scientific reports, vol. 6, 20030. https://doi.org/10.1038/srep20030

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title = "Multi-Organ toxicity demonstration in a functional human in vitro system composed of four organs",

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 {\^a} {\oe} human-on-a-chip{\^a} assay for systemic toxicity screening.",

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

note = "Funding Information: We would like to acknowledge support from the National Institutes of Health grant number UH2TR000516 and research collaboration and grant from L{\textquoteright}Oreal Corporation.",

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AU - Oleaga, Carlota

AU - Bernabini, Catia

AU - Smith, Alec S.T.

AU - Srinivasan, Balaji

AU - Jackson, Max

AU - McLamb, William

AU - Platt, Vivien

AU - Bridges, Richard

AU - Cai, Yunqing

AU - Santhanam, Navaneetha

AU - Berry, Bonnie

AU - Najjar, Sarah

AU - Akanda, Nesar

AU - Guo, Xiufang

AU - Martin, Candace

AU - Ekman, Gail

AU - Esch, Mandy B.

AU - Langer, Jessica

AU - Ouedraogo, Gladys

AU - Cotovio, Jose

AU - Breton, Lionel

AU - Shuler, Michael L.

AU - Hickman, James J.

N1 - Funding Information: We would like to acknowledge support from the National Institutes of Health grant number UH2TR000516 and research collaboration and grant from L’Oreal Corporation.

PY - 2016/2/3

Y1 - 2016/2/3

N2 - 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.

AB - 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.

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

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