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

Journal Article · Sat Oct 01 00:00:00 EDT 2011 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2011.07.013· OSTI ID:21587852

Lan, Shih-Feng ^[1]; Starly, Binil ^[1]

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1. University of Oklahoma Bioengineering Center, University of Oklahoma, Norman, OK 73019 (United States)

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.

• OSTI ID: 21587852
• Journal Information: Toxicology and Applied Pharmacology, Vol. 256, 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); ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

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