On Saturday, March 11, 2017, at the Horizons and Challenges in Organotypic Culture Models for Predictive Toxicology Satellite Meeting in Baltimore, the Human Models for Analysis of Pathways (HMAPs) Center will be presenting on emerging technologies and resources for predictive Toxicology. New toxicity testing methods include new microfluidic technologies for generating human tissues-on-a-chip (also known as microphysiological systems or organotypic cultures), generation of regionally-specified and functionally mature stem cells, novel biological network analysis paradigms, and imaging technologies.
Human Models for Analysis of Pathways (HMAPs) Center is an US EPA-sponsored Science to Achieve Results (STAR) center, based in the University of Wisconsin, Madison, that addresses the need for human, organotypic culture models that comply with the requirements of contemporary toxin screening and drug discovery (i.e., reproducibility, high throughput, transferability of data, clear mechanisms of action, defined adverse outcomes).
These technologies will provide a suitable alternative and reduce the number of animals required for in vivo studies reducing the overreliance on animal studies. Current in vivo animal models do not capture the biological diversity and complexity of human tissues and it is not possible to screen the tens of thousands of chemical compounds that are present in our environment in animal models. Similarly, there is a need for human models to validate drug efficacy and avoid drug induced toxicity, as greater than 90% of new drug candidates fail even after passing through the majority of the drug development pipeline.
The H-MAPs Center is committed to transforming chemical toxicity testing and drug discovery by taking advantage of advances in biology, biotechnology, and computer modeling. The overall objective of the center is to create transformative organotypic human models in formats that offer unique practical capabilities for toxin screening and pathway analysis.
The Horizons and Challenges in Organotypic Culture Models for Predictive Toxicology Satellite Meeting is focused on the ability to create microphysiological organotypic culture models, provide an opportunity for a paradigm shift, and the advancement of alternative, more public health relevant and efficient toxicity testing methods. These Organotypic Culture Models for Predictive Toxicology (OCM-PTs) will be faster, less costly, and more scientifically robust than many currently available methods. Refined assessment models of how organs and tissues respond to environmental chemicals, coupled with the rigorous requirements of contemporary toxicology screening, will be critical to informing implementation of the Frank R. Lautenberg Chemical Safety for the 21st Century Act, the amended Toxic Substances Control Act. The development of OCM-PTs is complicated by their highly interdisciplinary nature. New directions, challenges, and needs will be discussed in order to bridge the research disciplines needed to move the cutting-edge science on OCM-PTs forward.
Sessions will be held with young investigators from the OCM-PT Centers at the University of Wisconsin (Human Models for Analysis of Pathways Center), Vanderbilt University/University of Pittsburgh (the Vanderbilt-Pittsburgh Resource for Organotypic Models for Predictive Toxicology), University of Washington (the University of Washington Predictive Toxicology Center), Texas A&M/North Carolina State University (the Cardiotoxicity Adverse Outcome Pathway Center), and their collaborators in the Chemical Safety for Sustainability Program at the US EPA.
Satellite Meeting
Agenda
The Human MAPs Center Objectives are to:
- Generate human pluripotent stem cell-derived cells that properly represent the diverse phenotypic characteristics of developing or mature human somatic cells;
- Generate organotypic cell culture models that are robust and reproducible;
- Translate organotypic cell culture models to microscale systems for HTS;
- Combine genomic/epigenomic analyses with bioinformatics to gain molecular level insights into organotypic model assembly and the pathways influenced by toxins.
The H-MAPs Center brings together leading experts in human pluripotent stem cell biology, human development, and microscale tissue engineering to develop organotypic human models. The Center will also form organotypic human models in robust, innovative high throughput screening systems and identify mechanisms of action associated with toxicity using bioinformatics-based pathway analysis. Projects are currently focused on four main targets:
- Generation of regionally-specified neural progenitor cells representing the dorsoventral and rostrocaudal axis for region-specific toxicity testing in the central nervous system (Brain MAPs)
- Generation of a 3D high-throughput microfluidics model that captures the different stages of breast cancer development. (Cancer MAPs)
- Development of a 3D high-throughput and functionally mature human organotypic model of the liver (Liver MAPs).
- Manufacturing of a human 3D organotypic culture model of the neurovascular unit that comprises the essential cellular components of the blood brain barrier (Vascular MAPs).
For more information, please visit the HMAP Center website.