Liang-Hsin Chen
BME PhD Proposal Presentation

Date: 2024-05-01
Time: 1:00 PM-3:00 PM
Location / Meeting Link: EBB 4029 / https://gatech.zoom.us/j/97679308016?pwd=UHIxOXVyWDNkZXpOZnhjN2VHWjdKZz09

Committee Members:
Shuichi Takayama, PhD (Advisor); Nga Lee (Sally) Ng, PhD; Rabindra Tirouvanziam, PhD; Melissa L. Kemp, PhD; Jessica R. Murray, PhD


Title: A high-throughput air-blood barrier array model for acute inhalation toxicity

Abstract:
The adverse health effects of air pollution are a worldwide concern that requires urgent attention. However, due to the complexity and spatiotemporal diversity of the composition of air pollution, it is difficult to conclude the risk of air pollution without understanding the toxicity of individual components in the air. The development of risk assessment for inhaled substances is therefore important to fill this need. Widely used animal models could provide both local and systemic toxicity endpoints for inhalation risk assessment; however, the ethical concern and species-specific difference impede further development of animal study for inhalation toxicity. The EPA has recognized the value of in vitro model as substitutes of in vivo models for acute inhalation toxicity assessment. Current models unfortunately failed to fulfill both physiological relevant and high-throughput considerations. These models were either built with single cell type or 3D low-throughput platforms. To fill this gap, we proposed a high-throughput air-blood barrier array (ABBA) model cultured under air-liquid interface (ALI) condition with primary neutrophils incorporated for acute inflammation toxicity testing. The barrier integrity, cytokine production, and neutrophil transmigration will be examined and investigated as endpoints showing the hazard of inhaled substances. The effect of macrophages will also be incorporated into the present model to further mimic macrophage-mediated inflammatory responses induced by inhaled biological substances. Moreover, the self-limiting mechanisms of neutrophils during transmigration will be determined by time-lapse monitoring of neutrophils at different stages during neutrophil recruitment and the concentration of neutrophil-mediated cytokines. By investigating these mechanisms, we could confirm the application of using transmigrated neutrophil number as an endpoint for acute inhalation toxicity assessment in this model. With the development and identification of the high-throughput ABBA model, the proposed assay is expected to serve as a reliable model to evaluate the risk of different inhalation substances.