Key result
Animal models and human-based organ-on-chip platforms accelerate patient-specific modeling and therapeutic development in PAH.
Why the study?
Traditional preclinical models often overlook patient-specific pathophysiology, mutations, and sex-specific responses, creating translational gaps in pulmonary arterial hypertension therapeutic development.
A multi-platform and precision medicine-oriented approach integrating in vivo, ex vivo, and in vitro models is advocated to bridge preclinical insights with clinical outcomes in PAH.
Supports multi-platform PAH modeling; leaves open clinical outcome improvements pending validation.
Pulmonary arterial hypertension (PAH) is a progressive vascular disease characterized by sustained elevation of pulmonary arterial pressure, endothelial cell dysfunction, and right ventricular failure. A wide range of experimental animal models, including the monocrotaline model, Sugen combined with hypoxia, and pulmonary artery banding in large animals, have been pivotal in uncovering disease mechanisms such as vascular remodeling, metabolic dysregulation, and hypoxia-inducible signaling. More recently, human-based platforms, including induced pluripotent stem cell-derived vascular cells, organ-on-chip systems, and precision-cut lung slices, have emerged as powerful tools to model patient-specific pathophysiology and study pharmacological responses. These systems enable the interrogation of BMPR2 mutations, mitochondrial dysfunction, and sex-specific responses, factors often overlooked in traditional preclinical models. Moreover, integrating these platforms with omics technologies and comorbidity-driven experimental systems addresses key translational gaps. This review provides an overview of animal and human-based models used in PAH research and highlights emerging strategies to enhance their translational relevance. We advocate for a multi-platform and precision medicine-oriented approach that bridges preclinical insights with clinical outcomes to accelerate therapeutic development in PAH.
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Singh et al. (2025) conducted a review in Pulmonary arterial hypertension. Experimental animal models and human-based platforms, including organ-on-chip systems, provide essential tools to model patient-specific pathophysiology and accelerate therapeutic development in PAH.
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