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Pulmonary-arterial-hypertension (PAH)-on-a-chip: fabrication, validation and application
Taslim A Al-Hilal1, Ali Keshavarz, Hossam Kadry
1Department of Pharmaceutical Sciences, Texas Tech University Health Sciences Center, Jerry H. Hodge School of Pharmacy, 1300 Coulter Dr., Amarillo, 79119 Texas, USA. fakhrul.ahsan@ttuhsc.edu.
Lab on a Chip
|August 5, 2020
Summary
A novel microfluidic tissue chip accurately models human pulmonary arterial hypertension (PAH) by recreating its key pathologies. This advanced model offers new avenues for studying PAH mechanisms and testing potential therapies.
Area of Science:
- Biomedical Engineering
- Cardiovascular Research
- Disease Modeling
Background:
- Current animal and cellular models for pulmonary arterial hypertension (PAH) inadequately replicate human disease pathophysiology, including sex disparities and combinatorial study limitations.
- Existing models struggle to reproduce key hallmarks of PAH, hindering research into disease mechanisms and therapeutic development.
Purpose of the Study:
- To develop and validate a microengineered tissue chip model that accurately recapitulates human pulmonary arterial hypertension (PAH).
- To create a platform for studying PAH pathobiology, sex disparities, and therapeutic efficacy.
Main Methods:
- Fabrication of a microfluidic device mimicking the layered structure of a pulmonary artery.
- Co-culture of pulmonary arterial cells (PACs) including endothelial, smooth muscle, and adventitial cells within the device.
- Induction of PAH-like conditions and assessment of cellular responses to flow-induced stress.
Main Results:
- The tissue chip successfully recreated major PAH pathologies: intimal thickening, muscularization, arterial remodeling, and endothelial-to-mesenchymal transition.
- Flow-induced stress in control cells led to morphological changes and arterial remodeling, mimicking disease progression.
- The model demonstrated potential for investigating PAH sex disparities and evaluating anti-PAH drug efficacy.
Conclusions:
- The developed microfluidic tissue chip serves as a robust and accurate model for human pulmonary arterial hypertension (PAH).
- This platform facilitates research into PAH pathobiology, sex-based differences, and the testing of novel therapeutic strategies.
