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 "human-on-a-chip" assay for systemic toxicity screening.
authors.affiliation: NanoScience Technology Center, University of Central Florida, 12424 Research Parkway Suite 400, Orlando, FL 32828.
authors.forename: Carlota
authors.initials: C
authors.lastname: Oleaga
authors.affiliation: NanoScience Technology Center, University of Central Florida, 12424 Research Parkway Suite 400, Orlando, FL 32828.
authors.forename: Catia
authors.initials: C
authors.lastname: Bernabini
authors.affiliation: NanoScience Technology Center, University of Central Florida, 12424 Research Parkway Suite 400, Orlando, FL 32828.
authors.forename: Alec S T
authors.initials: AS
authors.lastname: Smith
authors.affiliation: NanoScience Technology Center, University of Central Florida, 12424 Research Parkway Suite 400, Orlando, FL 32828.
authors.forename: Balaji
authors.initials: B
authors.lastname: Srinivasan
authors.affiliation: NanoScience Technology Center, University of Central Florida, 12424 Research Parkway Suite 400, Orlando, FL 32828.
authors.forename: Max
authors.initials: M
authors.lastname: Jackson
authors.affiliation: NanoScience Technology Center, University of Central Florida, 12424 Research Parkway Suite 400, Orlando, FL 32828.
authors.forename: William
authors.initials: W
authors.lastname: McLamb
authors.affiliation: NanoScience Technology Center, University of Central Florida, 12424 Research Parkway Suite 400, Orlando, FL 32828.
authors.forename: Vivien
authors.initials: V
authors.lastname: Platt
authors.affiliation: NanoScience Technology Center, University of Central Florida, 12424 Research Parkway Suite 400, Orlando, FL 32828.
authors.forename: Richard
authors.initials: R
authors.lastname: Bridges
authors.affiliation: NanoScience Technology Center, University of Central Florida, 12424 Research Parkway Suite 400, Orlando, FL 32828.
authors.forename: Yunqing
authors.initials: Y
authors.lastname: Cai
authors.affiliation: NanoScience Technology Center, University of Central Florida, 12424 Research Parkway Suite 400, Orlando, FL 32828.
authors.forename: Navaneetha
authors.initials: N
authors.lastname: Santhanam
authors.affiliation: NanoScience Technology Center, University of Central Florida, 12424 Research Parkway Suite 400, Orlando, FL 32828.
authors.forename: Bonnie
authors.initials: B
authors.lastname: Berry
authors.affiliation: NanoScience Technology Center, University of Central Florida, 12424 Research Parkway Suite 400, Orlando, FL 32828.
authors.forename: Sarah
authors.initials: S
authors.lastname: Najjar
authors.affiliation: NanoScience Technology Center, University of Central Florida, 12424 Research Parkway Suite 400, Orlando, FL 32828.
authors.forename: Nesar
authors.initials: N
authors.lastname: Akanda
authors.affiliation: NanoScience Technology Center, University of Central Florida, 12424 Research Parkway Suite 400, Orlando, FL 32828.
authors.forename: Xiufang
authors.initials: X
authors.lastname: Guo
authors.affiliation: NanoScience Technology Center, University of Central Florida, 12424 Research Parkway Suite 400, Orlando, FL 32828.
authors.forename: Candace
authors.initials: C
authors.lastname: Martin
authors.affiliation: NanoScience Technology Center, University of Central Florida, 12424 Research Parkway Suite 400, Orlando, FL 32828.
authors.forename: Gail
authors.initials: G
authors.lastname: Ekman
authors.affiliation: Department of Biomedical Engineering, Cornell University, 115 and 305 Weill Hall, Ithaca, NY 14853.
authors.forename: Mandy B
authors.initials: MB
authors.lastname: Esch
authors.affiliation: L'Oreal Research and Innovation, Clark, NJ, 07666/ Aulnay sous Bois, France, 93600.
authors.forename: Jessica
authors.initials: J
authors.lastname: Langer
authors.affiliation: L'Oreal Research and Innovation, Aulnay sous Bois, France.
authors.forename: Gladys
authors.initials: G
authors.lastname: Ouedraogo
authors.affiliation: L'Oreal Research and Innovation, Aulnay sous Bois, France.
authors.forename: Jose
authors.initials: J
authors.lastname: Cotovio
authors.affiliation: L'Oreal Research and Innovation, Aulnay sous Bois, France.
authors.forename: Lionel
authors.initials: L
authors.lastname: Breton
authors.affiliation: Department of Biomedical Engineering, Cornell University, 115 and 305 Weill Hall, Ithaca, NY 14853.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Shuler
authors.affiliation: NanoScience Technology Center, University of Central Florida, 12424 Research Parkway Suite 400, Orlando, FL 32828.
authors.forename: James J
authors.initials: JJ
authors.lastname: Hickman
mesh_terms: D002460:Cell Line; D002478:Cells, Cultured; D018920:Coculture Techniques; D016895:Culture Media, Serum-Free; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D056945:Hep G2 Cells; D006801:Humans; D057026:Induced Pluripotent Stem Cells; D056656:Lab-On-A-Chip Devices; D008099:Liver / Q000166:cytology / Q000187:drug effects*; D008954:Models, Biological; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects*; D009474:Neurons / Q000166:cytology / Q000187:drug effects*
chemical_list: D016895:Culture Media, Serum-Free
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