PFI-TT: A novel human developmental toxicity assay platform using microfluidics

Regents Of The University Of Michigan - Ann Arbor, Ann Arbor MI

Investigators

Abstract

The broader impact/commercial potential of this Partnerships for Innovation - Technology Translation (PFI-TT) project provides an alternative to animal models for assessing the toxic effects of chemical compounds on human development using induced pluripotent stem cells. Despite being expensive, time consuming, and offering limited insights into human biology, animal models are the current gold standard for toxicity testing. However, human cells can be used to generate models of early human development and, by using these models to assess toxic effects, human-relevant toxicity data may be more more controllable, repeatable, and inexpensive. Such an alternative to animal models could reduce the costs of drug and chemical development, and as regulatory groups worldwide set goals for the reduction and eventual elimination of animal testing, drug and chemical development companies will need to adopt effective and efficient alternatives. The few platforms for assessing toxicity that exist in the market rely on metrics that are inadequate for predicting human toxicity. As such, platforms that more faithfully model human development may have impact on the toxicity testing market space. The proposed project seeks to develop a novel human stem cell-based microfluidic developmental toxicology platform, in which three-dimensional multicellular models are generated for toxicity testing. This project aims to conduct critical technological developments for this microfluidic toxicology platform to make it repeatable, controllable, and high-throughput while thoroughly characterizing its predictive power. Specifically, this project aims to integrate microfluidic organoid-generation technology with automated and commercially-available liquid handling systems to minimize operator influence and enable future scale-up of the experimental platform via multiple integrated platforms running in parallel. Additionally, this project aims to validate the predictive power of the platform by using it to test the effects of a comprehensive suite of compounds with known toxicities. The testing may be used to determine the range of compounds for which the platform is predictive, as well as to examine the effects of each compound on tissue morphology, cell marker expression, and metabolism. This data will be used to determine the predictive power of each metric in order to develop efficient tools and endpoints to expedite toxicological assessment of experiments. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.