An organ-on-chip model of pulmonary arterial hypertension identifies a BMPR2-SOX17-prostacyclin signaling axis

Alexander J Ainscough , Timothy J Smith , Maike Haensel , Christopher J Rhodes , Adam Fellows , Harry J Whitwell , Eleni Vasilaki , Kelly Gray, Adrian Freeman , Luke S Howard , John Wharton , Benjamin Dunmore , Paul D Upton , Martin R Wilkins , Joshua B Edel, Beata Wojciak-Stothard 
Source: Nat Commun.
Publication Date: (2022)
Issue: 5: 1192
Research Area:
Respiratory Research
Cells used in publication:
SMC, pul.artery (PASMC), human
Species: human
Tissue Origin: artery

Cell culture 

HPASMCs (Lonza, Cat. No. CC-2581) were cultured in T75 tissue culture flasks coated with 0.2% porcine gelatin (Sigma, Cat. no. G1890) in smooth muscle cell growth medium 2 (SmGM-2, PromoCell, Cat. no. C-22062), supplemented with 5% FBS and growth factor supplement (PromoCell, Cat. no. C-39267) and antibiotics. Cells were acquired at passage 3 and were used for experiments in passages 4–6. Donor information is provided in Supplementary Table 2. For HPAEC and HPASMC co-culture, ECGM-2 medium was supplemented with 10% foetal bovine serum (FBS). VEGF, ascorbic acid, heparin, and hydrocortisone, known to inhibit HPASMC proliferation, were excluded.

Blood-derived human endothelial cells 

... ECFCs were cultured in 1% porcine gelatin-coated T75 tissue culture flasks (Sigma, Cat. no. G1890) in EGM-2 medium (CC-3156, Lonza Biologics, Slough, UK), supplemented with growth factors (CC-4176, EGMTM-2 bullet kit, Lonza), 10% FBS (HyClone, Thermo Scientific, South Logan, UT, USA) and 1% antibiotic/antimycotic solution (Gibco, Invitrogen, Paisley, UK). All ECFCs were used between passages 3 and 6.


Pulmonary arterial hypertension (PAH) is an unmet clinical need. The lack of models of human disease is a key obstacle to drug development. We present a biomimetic model of pulmonary arterial endothelial-smooth muscle cell interactions in PAH, combining natural and induced bone morphogenetic protein receptor 2 (BMPR2) dysfunction with hypoxia to induce smooth muscle activation and proliferation, which is responsive to drug treatment. BMPR2- and oxygenation-specific changes in endothelial and smooth muscle gene expression, consistent with observations made in genomic and biochemical studies of PAH, enable insights into underlying disease pathways and mechanisms of drug response. The model captures key changes in the pulmonary endothelial phenotype that are essential for the induction of SMC remodelling, including a BMPR2-SOX17-prostacyclin signalling axis and offers an easily accessible approach for researchers to study pulmonary vascular remodelling and advance drug development in PAH.