Modeling aortic diseases using induced pluripotent stem cells

Abstract

Abstract Induced pluripotent stem cells (iPSCs) offer an effective platform for studies of human physiology and have revealed new possibilities for disease modeling at the cellular level. These cells also have the potential to be leveraged in the practice of precision medicine, including personalized drug testing. Aortic diseases result in significant morbidity and mortality and pose a global burden to healthcare. Their pathogenesis is mostly associated with functional alterations of vascular components, such as endothelial cells and vascular smooth muscle cells. Drugs that have been proven to be effective in animal models often fail to protect patients from adverse aortic events in clinical studies, provoking researchers to develop reliable in vitro models using human cells. In this review, we summarize the patient iPSC-derived aortic cells that have been utilized to model aortic diseases in vitro. In advanced models, hemodynamic factors, such as blood flow-induced shear stress and cyclic strain, have been added to the systems to replicate cellular microenvironments in the aortic wall. Examples of the utility of such factors in modeling various aortopathies, such as Marfan syndrome, Loeys-Dietz syndrome, and bicuspid aortic valve-related aortopathy, are also described. Overall, the iPSC-based in vitro cell models have shown the potential to promote the development and practice of precision medicine in the treatment of aortic diseases.