Grantee Research Project Results
Final Report: Developmental Neurotox Assay Using Scalable Neurons and Astrocytes in High-Content Imaging
EPA Contract Number: EPD13018Title: Developmental Neurotox Assay Using Scalable Neurons and Astrocytes in High-Content Imaging
Investigators: Majumder, Anirban
Small Business: ArunA Biomedical, Inc.
EPA Contact: Richards, April
Phase: I
Project Period: May 15, 2013 through November 14, 2013
Project Amount: $79,993
RFA: Small Business Innovation Research (SBIR) - Phase I (2013) RFA Text | Recipients Lists
Research Category: Small Business Innovation Research (SBIR) , SBIR - Innovation in Manufacturing
Description:
There is a stated need both within the computational toxicology programs at EPA and regulatory agencies worldwide for rapid, cost effective in vitro methods to identify chemicals that pose a hazard to the developing human brain. As an alternative to costly animal studies, a number of in vitro assays utilizing primary cell lines have been tested in an effort to find and devise effective models to prioritize chemicals for further in depth toxicity studies. However, isolation of primary neural tissue is cost- and labor-intensive, and primary cells cannot be produced in the numbers required for high throughput screening (HTS). To address this critical cell sourcing limitation, ArunA Biomedical has developed HTS-scalable, human embryonic stem cell (hESC) derived cellular model systems, hNP1™ Human Neural Progenitor Cells and hN2™ Differentiated Human Neuronal Cells, which are commercially available to advance developmental neurotoxicity assays. It has been increasingly appreciated that multi-cellular systems provide a more physiologically relevant in vitro system to assess the effect of drug candidates on complex tissue systems. In this project, the company addressed this major gap by developing a multi-cellular neural system [neurons (hN2™) and astrocytes, referred to as AstroPro™], that more faithfully recapitulates early neural development. Moreover, the use of pluripotent progenitor cells enables scalable, high content screening (HCS)-amenable formats for toxicant screening and adverse outcome pathway computational analyses. In this study, ArunA Biomedical assessed the feasibility of using a neuron-astrocyte co-culture system for high throughput neurotoxicity screening, and reinforced the need for a more representative system by demonstrating that known neurotoxins do indeed evoke different neuronal responses in a multi-cellular assay environment.
Summary/Accomplishments (Outputs/Outcomes):
Conclusions:
Supplemental Keywords:
astrocytes, neurons, neurotoxicology, stem cells, neurotoxicity assayRelevant Websites:
SBIR Phase II:
Developmental Neurotox Assay using Scalable Neurons and Astrocytes in High Content Imaging | Final ReportThe perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.