Endothelial-smooth muscle microgauges for modeling pulmonary arterial vasoregulation

Area of Science:

• Cardiovascular Biology
• Biomedical Engineering
• Vascular Physiology

Background:

• Pulmonary arterial hypertension (PAH) is a severe condition with no cure, characterized by endothelial dysfunction and altered vascular tone.
• Current limitations in animal models and human in vitro systems hinder the development of effective PAH therapeutics.
• Understanding endothelial-dependent regulation of smooth muscle cell contractility is crucial for PAH research.

Purpose of the Study:

• To develop a novel humanized in vitro system for studying pulmonary arterial hypertension (PAH).
• To create a platform for quantifying endothelial-dependent smooth muscle cell contractility in pulmonary arteries.
• To facilitate the screening of potential therapeutics for PAH and related hypertensive diseases.

Main Methods:

• Microfabrication of pulmonary artery smooth muscle microgauges (PA-SMUGs) to create microtissues.
• Incorporation of a functional monolayer of pulmonary arterial endothelial cells (PAECs) within the microtissues.
• Quantification of contractile forces generated by human pulmonary arterial smooth muscle cells (PASMCs).

Main Results:

• The PA-SMUGs platform successfully demonstrated pulmonary arterial endothelial cell (PAEC)-dependent vasorelaxation.
• The microgauges responded to treprostinil, a known therapeutic agent for PAH.
• This system provides a high-throughput method for assessing endothelial-dependent vasorelaxation.

Conclusions:

• The developed PA-SMUGs platform offers a valuable humanized in vitro model for PAH research.
• This system enables mechanistic studies on the crosstalk between PAECs and PASMCs in PAH pathogenesis.
• The platform facilitates high-throughput screening for novel therapeutics to improve outcomes in PAH and other hypertensive diseases.