Pulmonary-arterial-hypertension (PAH)-on-a-chip: fabrication, validation and application

Taslim A. Al-Hilal; Ali Keshavarz; Hossam Kadry; Behnaz Lahooti; Ahmed Al-Obaida; Zhenya Ding; Wei Li; Roger Kamm; Ivan F. McMurtry; Tim Lahm; Eva Nozik-Grayck; Kurt R. Stenmark; Fakhrul Ahsan

doi:10.1039/D0LC00605J

Pulmonary-arterial-hypertension (PAH)-on-a-chip: fabrication, validation and application†

Taslim A. Al-Hilal,‡^a Ali Keshavarz,^a Hossam Kadry,§^a Behnaz Lahooti,§^a Ahmed Al-Obaida,^a Zhenya Ding,^b Wei Li,

^b Roger Kamm,

^cd Ivan F. McMurtry,^e Tim Lahm,^fg Eva Nozik-Grayck,^h Kurt R. Stenmark^h and Fakhrul Ahsan

*^a

Author affiliations

* Corresponding authors

^a Department of Pharmaceutical Sciences, Texas Tech University Health Sciences Center, Jerry H. Hodge School of Pharmacy, 1300 Coulter Dr., Amarillo, 79119 Texas, USA
E-mail: fakhrul.ahsan@ttuhsc.edu
Fax: +1 806 356 4034
Tel: +1 806 414 9235

^b Department of Chemical Engineering, Texas Tech University, Lubbock, Texas, USA

^c Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA

^d Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA

^e Department of Pharmacology, The Center for Lung Biology, University of South Alabama, Mobile, AL 36688, USA

^f Department of Pulmonary and Critical Care, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA

^g Richard L. Roudebush Veterans Affairs Medical Center, Indianapolis, Indiana, USA

^h Department of Pediatrics and Medicine, Cardiovascular Pulmonary Research Laboratories, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO 80045, USA

Abstract

Currently used animal and cellular models for pulmonary arterial hypertension (PAH) only partially recapitulate its pathophysiology in humans and are thus inadequate in reproducing the hallmarks of the disease, inconsistent in portraying the sex-disparity, and unyielding to combinatorial study designs. Here we sought to deploy the ingenuity of microengineering in developing and validating a tissue chip model for human PAH. We designed and fabricated a microfluidic device to emulate the luminal, intimal, medial, adventitial, and perivascular layers of a pulmonary artery. By growing three types of pulmonary arterial cells (PACs)-endothelial, smooth muscle, and adventitial cells, we recreated the PAH pathophysiology on the device. Diseased (PAH) PACs, when grown on the chips, moved of out their designated layers and created phenomena similar to the major pathologies of human PAH: intimal thickening, muscularization, and arterial remodeling and show an endothelial to mesenchymal transition. Flow-induced stress caused control cells, grown on the chips, to undergo morphological changes and elicit arterial remodeling. Our data also suggest that the newly developed chips can be used to elucidate the sex disparity in PAH and to study the therapeutic efficacy of existing and investigational anti-PAH drugs. We believe this miniaturized device can be deployed for testing various prevailing and new hypotheses regarding the pathobiology and drug therapy in human PAH.

Lab on a Chip

Pulmonary-arterial-hypertension (PAH)-on-a-chip: fabrication, validation and application†

Abstract

Supplementary files

Article information

Download Citation

Permissions

Pulmonary-arterial-hypertension (PAH)-on-a-chip: fabrication, validation and application

Social activity

Search articles by author

Spotlight

Advertisements