ArticleAmerican journal of respiratory and critical care medicine2017
Induced Pluripotent Stem Cell Model of Pulmonary Arterial Hypertension Reveals Novel Gene Expression and Patient Specificity.
Article in American journal of respiratory and critical care medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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62 citing papers in PubMed, 92 citations in OpenAlex.
- Human iPSC-Derived Vascularised Lung Organoids for Modelling COPD and Pulmonary Hypertension.Cell proliferation · 2026Article
- High-Throughput Digital Decoding of Vascular Heterogeneity in Patient-Specific Tumor Microenvironments.Advanced healthcare materials · 2026Article
- KLF6 activation marks an angiogenic and apoptosis resistant endothelial phenotype in pulmonary arterial hypertension.Communications biology · 2026Article
- Investigational New Drug-enabling studies in a human vessel-chip: Are we there yet?Bioengineering & translational medicine · 2026Review
- Vascularized Cardiac Tissue Engineering: From Advances in Biofabrication to Translational Applications.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Echocardiographic hemodynamics correlate with differences in DOAC-specific bleeding and stroke rates in non-valvular atrial fibrillation.BMC cardiovascular disorders · 2025Article
- Role of BMPR2 Mutation in Lung Organoid Differentiation.Biomedicines · 2025Article
- Predicting Response to Switching From Phosphodiesterase Type 5 Inhibitor to Riociguat in Patients With Pulmonary Arterial Hypertension: Biomarker and Responder Analysis of the RESPITE and REPLACE Studies.Pulmonary circulation · 2025Article
- From basic scientific research to the development of new drugs for pulmonary arterial hypertension: insights from activin-targeting agents.Breathe (Sheffield, England) · 2025Review
- Building a human lung from pluripotent stem cells to model respiratory viral infections.Respiratory research · 2024Review
- Novel insights into the potential applications of stem cells in pulmonary hypertension therapy.Respiratory research · 2024Review
- Understanding genomic medicine for thoracic aortic disease through the lens of induced pluripotent stem cells.Frontiers in cardiovascular medicine · 2024Review
- Unraveling the Role of Sex in Endothelial Cell Dysfunction: Evidence From Lineage Tracing Mice and Cultured Cells.Arteriosclerosis, thrombosis, and vascular biology · 2024Article
- Transcriptional profiles of pulmonary artery endothelial cells in pulmonary hypertension.Scientific reports · 2023Article
- Stem cell therapy in pulmonary hypertension: current practice and future opportunities.European respiratory review : an official journal of the European Respiratory Society · 2023Review
- Review
- Article
- E-cigarettes Induce Dysregulation of Autophagy Leading to Endothelial Dysfunction in Pulmonary Arterial Hypertension.Stem cells (Dayton, Ohio) · 2023Article
- Clinical Translation of Engineered Pulmonary Vascular Models.Advances in experimental medicine and biology · 2023Article
- Review
2 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 3 institutions in 2 countries.
Funding
Abstract
rationaleIdiopathic or heritable pulmonary arterial hypertension is characterized by loss and obliteration of lung vasculature. Endothelial cell dysfunction is pivotal to the pathophysiology, but different causal mechanisms may reflect a need for patient-tailored therapies.
objectivesEndothelial cells differentiated from induced pluripotent stem cells were compared with pulmonary arterial endothelial cells from the same patients with idiopathic or heritable pulmonary arterial hypertension, to determine whether they shared functional abnormalities and altered gene expression patterns that differed from those in unused donor cells. We then investigated whether endothelial cells differentiated from pluripotent cells could serve as surrogates to test emerging therapies.
methodsFunctional changes assessed included adhesion, migration, tube formation, and propensity to apoptosis. Expression of bone morphogenetic protein receptor type 2 (BMPR2) and its target, collagen IV, signaling of the phosphorylated form of the mothers against decapentaplegic proteins (pSMAD1/5), and transcriptomic profiles were also analyzed. MEASUREMENTS AND MAIN
resultsNative pulmonary arterial and induced pluripotent stem cell-derived endothelial cells from patients with idiopathic and heritable pulmonary arterial hypertension compared with control subjects showed a similar reduction in adhesion, migration, survival, and tube formation, and decreased BMPR2 and downstream signaling and collagen IV expression. Transcriptomic profiling revealed high kisspeptin 1 (KISS1) related to reduced migration and low carboxylesterase 1 (CES1), to impaired survival in patient cells. A beneficial angiogenic response to potential therapies, FK506 and Elafin, was related to reduced slit guidance ligand 3 (SLIT3), an antimigratory factor.
conclusionsDespite the site of disease in the lung, our study indicates that induced pluripotent stem cell-derived endothelial cells are useful surrogates to uncover novel features related to disease mechanisms and to better match patients to therapies.
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