Modeling pulmonary arterial hypertension using induced pluripotent stem cells

Amer A. Rana, Fedir N. Kiskin, C. Hong Chang

Research output: Chapter in Book/Report/Conference proceedingChapter


Heritable pulmonary arterial hypertension belongs to a group of pulmonary vascular diseases for which there is currently no cure other than a heart and lung transplantation. Increased endothelial and smooth muscle cell proliferation leads to vascular remodeling, resulting in increased blood pressure in the lungs which ultimately causes right heart failure. Understanding the molecular mechanisms implicated in the establishment and progression of pulmonary arterial hypertension is hampered due to a lack of disease models, including a limited availability of patient-derived cells and the low penetrance of BMPR2, the major disease-associated gene. Induced pluripotent stem cells provide a series of advantages for disease modeling that could potentially allow theses issues to be overcome. These include (1) a limitlessly self-renewing capacity that overcomes the restricted supply of cells from diseased patients, (2) an epigenome that has been wiped of pathogenic modifications which have accumulated during the disease process, (3) an amenability to gene editing which allows the introduction of specific pathogenic mutations in an otherwise isogenic background to facilitate the dissection of the precise contribution of disease-associated genetic mutations, and (4) the generation of isogenic cell, tissue, and organ-specific disease models.

Original languageEnglish
Title of host publicationMolecular Mechanism of Congenital Heart Disease and Pulmonary Hypertension
PublisherSpringer Nature Singapore
Number of pages7
ISBN (Electronic)9789811511851
ISBN (Print)9789811511844
Publication statusPublished - 1 Jan 2020


  • BMPR2
  • Disease modeling
  • Induced pluripotent stem cells
  • Pulmonary arterial hypertension
  • Smooth muscle and endothelial cells

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