External collaborations
Toxicity testing
Toxicity testing in 21 century requires the development of high throughput, in vitro assays to replace/reduce/refine the animal testing. xCELLigence system is a great platform for that purpose. Un-manipulated in vitro cell lines or primary cells are continuously monitored, providing high abundant information over the entire time course, which mimic the continuous monitoring of animal responses rather than an end point. Currently, ACEA Biosciences inc. is working with 2 partners on environmental toxicity testing.
US EPA-ToxCast Program
ACEA Biosciences Inc. has been awarded under EPA ToxCast program since it was initially launched in 2007. ACEA’s patented Real-time Cell Electronic Sensing technology provides an assay platform to effectively screen undisturbed live cell response profiles. These assays align well with ToxCast program goal, which is to develop ways to predict potential toxicity and to develop a fast and cost-effective approach for prioritizing the thousands of chemicals that need toxicity testing. Currently, ACEA has completed phase I cytotoxicity screening of 320 compounds. The results are available in ToxCast database . For phase II testing of 700 compounds, EPA adopted one of ACEA newly developed assays for accurately detecting estrogen/progesterone mimics, while obtaining cytotoxicity data at the same time. The screening work has been finished. EPA will analyze and compile the data from other assays, and publish in the future.
Human breast cancer cell line T-47D expresses both estrogen receptors and progesterone receptors . T-47D cells were seeded in 96 E-plate, and monitored on xCELLigence system. After overnight growth, T-47D cells were tested for responses to 2 different hormones: 17β-estradiol (E2) and progesterone (Pg). As shown by the red lines in the figures, E2 and Pg induce distinctive kinetic response profiles captured on xCELLigence system. Estrogen antagonist ICI182780 specifically abolish E2, but not Pg, caused responses (blue lines).
Collaboration with ACFT, Canada
ACEA Biosciences, Inc. and Alberta Center For Toxicology, University of Calgary, Canada signed an agreement in 2009, to develop new human risk assessment model based on in vitro cytotoxicity assays. Human cell panels representing important organ and functions will be selected, and tested on xCELLigence system for real time monitoring cellular responses to environmental toxins. Preliminary testing indicated that the new assays generate data of high quality, high reproducibility, and of high prediction values for in vivo toxicity. A big advantage of assays on xCELLigence system is that time-dependant cell response profile (TCRP) curves reflect different mechanism of actions. Further work is underway to develop tools making use of TCRP curve for toxicity pathway identification.