A 3-D tissue model for high-throughput drug discovery

BIOT 452

Xudong Zhang, zhangx@chbmeng.ohio-state.edu, Department of Chemical and Biomolecular Engineering, The Ohio State University, 140 West 19th Ave., Columbus, OH 43210, Robin Ng, ng.128@osu.edu, Department of Chemical Engineering, Ohio State University, 140 West 19th Ave., Koffolt Lab, Columbus, OH 43210, and Shang-tian Yang, yang.15@osu.edu, Dept. of Chemical Engineering, Ohio State University, 140 W.19th Ave, Columbus, OH 43210.
3D tissue model can mimick in-vivo tissue environment and provide bioactivity information in HTS fashion, facilitating selection of better drug candidates for further animal experiments. A high-throughput, real-time, bioactivity assay based on 3D cultures of green fluorescent protein (GFP)-expressing cells was developed. The system containing 40 microbioreactors on a 384-well plate can be used for cytotoxicity and proliferation assays in both high-density and low-density 3D cultures. To test this new 3D microbioreactor array for HTS drug screening, a colon cancer cell line was used to study the efficacy of several commonly used cancer drugs, including 5-fluorouracil and gemcitabine. The results from high-density 3D cultures matched with clinical effects of these drugs, whereas conventional 2D monolayer cultures errorneously predicted a much lower effective drug dosage. Thus, the 3D microbioreactor array has a great potential for improving the drug discovery process.