Related Experiment Video
Updated: Jul 29, 2025
08:59
Utilizing the Precision-Cut Lung Slice to Study the Contractile Regulation of Airway and Intrapulmonary Arterial Smooth Muscle
Published on: May 5, 2022
3.5K
A high-throughput 3D cantilever array to model airway smooth muscle hypercontractility in asthma
Pranjali Beri1, Christopher Plunkett1, Joshua Barbara1
1Novartis Institutes for Biomedical Research, San Diego, California 92121, USA.
APL Bioengineering
|May 19, 2023
Summary
A new 3D microtissue model of asthma was developed to study airway hypercontractility. This model identified inflammatory cytokines that cause asthma phenotypes and screened kinase inhibitors for potential therapeutics.
Area of Science:
- Biomedical Engineering
- Respiratory Medicine
- Pharmacology
Background:
- Asthma involves airway remodeling and hypercontraction, driven by smooth muscle.
- Current therapies offer symptom relief but don't halt disease progression or improve baseline airway narrowing.
- Advanced models are needed to study asthma's 3D tissue environment and contractility for drug discovery.
Purpose of the Study:
- To develop a high-throughput 3D in vitro model for studying asthma.
- To identify inflammatory triggers of airway smooth muscle hypercontractility.
- To screen kinase inhibitors for potential asthma therapeutics.
Main Methods:
- Development of DEFLCT, a plate insert for generating microscale airway tissues.
- Exposure of human airway smooth muscle microtissues to inflammatory cytokines.
- RNA sequencing and screening of kinase inhibitors on treated tissues.
Main Results:
- DEFLCT platform successfully generated 3D microtissues for screening.
- Transforming growth factor-beta 1 (TGF-β1) and Interleukin-13 (IL-13) induced hypercontractility.
- Protein kinase C (PKC) and mTOR/Akt signaling inhibition prevented hypercontractility, while myosin light chain kinase (MLCK) inhibition did not.
Conclusions:
- The DEFLCT platform provides a disease-relevant 3D model for asthmatic airway research.
- TGF-β1 and IL-13 are key inflammatory drivers of asthma-related hypercontractility.
- Targeting PKC and mTOR/Akt signaling pathways shows promise for preventing airway hypercontraction in asthma drug discovery.
