Modeling aortic diseases using induced pluripotent stem cells.
Kai ZhuWenrui MaJun LiYu Shrike ZhangWeijia ZhangHao LaiChunsheng WangPublished in: Stem cells translational medicine (2020)
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.
Keyphrases
- aortic valve
- induced pluripotent stem cells
- transcatheter aortic valve replacement
- aortic stenosis
- transcatheter aortic valve implantation
- aortic valve replacement
- healthcare
- endothelial cells
- blood flow
- vascular smooth muscle cells
- aortic dissection
- primary care
- left ventricular
- case report
- end stage renal disease
- pulmonary artery
- induced apoptosis
- stem cells
- drug induced
- heart failure
- chronic kidney disease
- emergency department
- cell cycle arrest
- angiotensin ii
- single cell
- ejection fraction
- coronary artery
- cell death
- peritoneal dialysis
- coronary artery disease
- patient reported
- oxidative stress
- replacement therapy
- high throughput
- risk assessment