Contributions of BMPR2 Mutations and Extrinsic Factors to Cellular Phenotypes of Pulmonary Arterial Hypertension Revealed by Induced Pluripotent Stem Cell Modeling

[...]other phenotypes such as inner mitochondrial membrane (IMM) hyperpolarization could not be recapitulated. [...]there is a need to better understand the contribution of BMPR2 mutations to PAH-associated phenotypes and the requirement for other factors in this process. Derivation of iPSC-SMCs and iPSC-ECs that perfectly represent adult PASMCs and PAECs is yet to be achieved. [...]our goal was to generate iPSC-SMCs that recapitulated some of the important functional responses of adult-derived distal PASMCs, as well as iPSCECs with enhanced expression of arterial markers, that could be used as surrogates for adult pulmonary vascular cells. [...]these protocols will have a broad effect for those modeling pulmonary vascular diseases, and also for those using pulmonary organoids and pulmonary artery-on-chip technologies to study epithelial-endothelial cell interactions in the alveoli and for drug screening. [...]this study defines an iPSC-derived SMC model of PAH.