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Updated: Dec 26, 2025
Author Spotlight: Advancing 3D Cell Modeling – A High-Throughput Approach for Neural Cocultures
Published on: September 29, 2023
Three-dimensional brain-on-chip model using human iPSC-derived GABAergic neurons and astrocytes:
Lumei Liu1, Youngmi Koo1, Teal Russell1
1FIT BEST Laboratory, Department of Chemical, Biological, and Bio Engineering, North Carolina Agricultural and Technical State University, Greensboro, North Carolina, United States of America.
Abstract:
Organophosphates (OPs) induce acute and chronic neurotoxicity, primarily by inhibiting acetylcholinesterase (AChE) activity as well as by necrosis, and apoptosis. Butyrylcholinesterase (BuChE), an exogenous bioscavenger of OPs, can be used as a treatment for OP exposure. It is prerequisite to develop in vitro brain models that can study BuChE post-treatment for acute OP exposure. In this study, we developed a three-dimensional (3D) brain-on-chip platform with human induced pluripotent stem cell (iPSC)-derived neurons and astrocytes to simulate human brain behavior. The platform consists of two compartments: 1) a hydrogel embedded with human iPSC-derived GABAergic neurons and astrocytes and 2) a perfusion channel with dynamic medium flow. The brain tissue constructs were exposed to Malathion (MT) at various concentrations and then treated with BuChE after 20 minutes of MT exposure. Results show that the iPSC-derived neurons and astrocytes directly interacted and formed synapses in the 3D matrix, and that treatment with BuChE improved viability after MT exposure up to a concentration of 10-3 M. We conclude that the 3D brain-on-chip platform with human iPSC-derived brain cells is a suitable model to study the neurotoxicity of OP exposure and evaluate therapeutic compounds for treatment.
Insights
A novel 3D brain-on-chip model using human stem cells effectively simulates organophosphate neurotoxicity. This platform shows butyrylcholinesterase (BuChE) can protect brain cells from Malathion (MT) exposure.
Area of Science:
- Neuroscience
- Toxicology
- Biotechnology
Background:
- Organophosphates (OPs) cause significant neurotoxicity by inhibiting acetylcholinesterase (AChE).
- Butyrylcholinesterase (BuChE) shows potential as an exogenous bioscavenger for OP poisoning treatment.
- Developing in vitro brain models is crucial for studying BuChE efficacy post-acute OP exposure.
Purpose of the Study:
- To develop a 3D brain-on-chip platform using human induced pluripotent stem cell (iPSC)-derived cells.
- To simulate human brain responses to acute organophosphate exposure.
- To evaluate the therapeutic potential of BuChE in this model.
Main Methods:
- A 3D brain-on-chip platform was created with iPSC-derived GABAergic neurons and astrocytes in a hydrogel.
- The platform featured a perfusion channel for dynamic medium flow.
- Constructs were exposed to Malathion (MT) and subsequently treated with BuChE.
Main Results:
- iPSC-derived neurons and astrocytes formed synaptic connections within the 3D matrix.
- BuChE treatment significantly improved cell viability following MT exposure up to 10⁻³ M.
- The model successfully mimicked key aspects of OP neurotoxicity and therapeutic response.
Conclusions:
- The developed 3D brain-on-chip platform is a viable model for studying OP neurotoxicity.
- This platform can be used to assess the efficacy of therapeutic agents like BuChE.
- Human iPSC-derived brain cells in a 3D matrix provide a robust system for neurotoxicity research.
