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Title: Alginate based 3D hydrogels as an in vitro co-culture model platform for the toxicity screening of new chemical entities

Abstract

Prediction of human response to potential therapeutic drugs is through conventional methods of in vitro cell culture assays and expensive in vivo animal testing. Alternatives to animal testing require sophisticated in vitro model systems that must replicate in vivo like function for reliable testing applications. Advancements in biomaterials have enabled the development of three-dimensional (3D) cell encapsulated hydrogels as in vitro drug screening tissue model systems. In this study, we have developed an in vitro platform to enable high density 3D culture of liver cells combined with a monolayer growth of target breast cancer cell line (MCF-7) in a static environment as a representative example of screening drug compounds for hepatotoxicity and drug efficacy. Alginate hydrogels encapsulated with serial cell densities of HepG2 cells (10{sup 5}-10{sup 8} cells/ml) are supported by a porous poly-carbonate disc platform and co-cultured with MCF-7 cells within standard cell culture plates during a 3 day study period. The clearance rates of drug transformation by HepG2 cells are measured using a coumarin based pro-drug. The platform was used to test for HepG2 cytotoxicity 50% (CT{sub 50}) using commercially available drugs which further correlated well with published in vivo LD{sub 50} values. The developed test platform allowedmore » us to evaluate drug dose concentrations to predict hepatotoxicity and its effect on the target cells. The in vitro 3D co-culture platform provides a scalable and flexible approach to test multiple-cell types in a hybrid setting within standard cell culture plates which may open up novel 3D in vitro culture techniques to screen new chemical entity compounds. - Graphical abstract: Display Omitted Highlights: > A porous support disc design to support the culture of desired cells in 3D hydrogels. > Demonstrated the co-culture of two cell types within standard cell-culture plates. > A scalable, low cost approach to toxicity screening involving multiple cell types.« less

Authors:
 [1];  [1];  [2]
  1. University of Oklahoma Bioengineering Center, University of Oklahoma, Norman, OK 73019 (United States)
  2. (United States)
Publication Date:
OSTI Identifier:
21587852
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 256; Journal Issue: 1; Other Information: DOI: 10.1016/j.taap.2011.07.013; PII: S0041-008X(11)00282-1; Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ALGINATES; CELL CULTURES; COUMARIN; FORECASTING; HYDROGELS; IN VITRO; IN VIVO; LIVER CELLS; MAMMARY GLANDS; NEOPLASMS; TESTING; TOXICITY; ANIMAL CELLS; ANTICOAGULANTS; BODY; COLLOIDS; DISEASES; DISPERSIONS; DRUGS; ESTERS; GELS; GLANDS; HEMATOLOGIC AGENTS; HETEROCYCLIC COMPOUNDS; HETEROCYCLIC OXYGEN COMPOUNDS; LACTONES; ORGANIC COMPOUNDS; ORGANIC OXYGEN COMPOUNDS; ORGANS; PYRANS; SOMATIC CELLS

Citation Formats

Lan, Shih-Feng, Starly, Binil, E-mail: starlyb@ou.edu, and School of Industrial Engineering, University of Oklahoma, Norman, OK 73019. Alginate based 3D hydrogels as an in vitro co-culture model platform for the toxicity screening of new chemical entities. United States: N. p., 2011. Web. doi:10.1016/j.taap.2011.07.013.
Lan, Shih-Feng, Starly, Binil, E-mail: starlyb@ou.edu, & School of Industrial Engineering, University of Oklahoma, Norman, OK 73019. Alginate based 3D hydrogels as an in vitro co-culture model platform for the toxicity screening of new chemical entities. United States. doi:10.1016/j.taap.2011.07.013.
Lan, Shih-Feng, Starly, Binil, E-mail: starlyb@ou.edu, and School of Industrial Engineering, University of Oklahoma, Norman, OK 73019. Sat . "Alginate based 3D hydrogels as an in vitro co-culture model platform for the toxicity screening of new chemical entities". United States. doi:10.1016/j.taap.2011.07.013.
@article{osti_21587852,
title = {Alginate based 3D hydrogels as an in vitro co-culture model platform for the toxicity screening of new chemical entities},
author = {Lan, Shih-Feng and Starly, Binil, E-mail: starlyb@ou.edu and School of Industrial Engineering, University of Oklahoma, Norman, OK 73019},
abstractNote = {Prediction of human response to potential therapeutic drugs is through conventional methods of in vitro cell culture assays and expensive in vivo animal testing. Alternatives to animal testing require sophisticated in vitro model systems that must replicate in vivo like function for reliable testing applications. Advancements in biomaterials have enabled the development of three-dimensional (3D) cell encapsulated hydrogels as in vitro drug screening tissue model systems. In this study, we have developed an in vitro platform to enable high density 3D culture of liver cells combined with a monolayer growth of target breast cancer cell line (MCF-7) in a static environment as a representative example of screening drug compounds for hepatotoxicity and drug efficacy. Alginate hydrogels encapsulated with serial cell densities of HepG2 cells (10{sup 5}-10{sup 8} cells/ml) are supported by a porous poly-carbonate disc platform and co-cultured with MCF-7 cells within standard cell culture plates during a 3 day study period. The clearance rates of drug transformation by HepG2 cells are measured using a coumarin based pro-drug. The platform was used to test for HepG2 cytotoxicity 50% (CT{sub 50}) using commercially available drugs which further correlated well with published in vivo LD{sub 50} values. The developed test platform allowed us to evaluate drug dose concentrations to predict hepatotoxicity and its effect on the target cells. The in vitro 3D co-culture platform provides a scalable and flexible approach to test multiple-cell types in a hybrid setting within standard cell culture plates which may open up novel 3D in vitro culture techniques to screen new chemical entity compounds. - Graphical abstract: Display Omitted Highlights: > A porous support disc design to support the culture of desired cells in 3D hydrogels. > Demonstrated the co-culture of two cell types within standard cell-culture plates. > A scalable, low cost approach to toxicity screening involving multiple cell types.},
doi = {10.1016/j.taap.2011.07.013},
journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 1,
volume = 256,
place = {United States},
year = {2011},
month = {10}
}