Modeling Blood-Brain Barrier Integrity and Hemodynamics in Autism Spectrum Disorder with an iPSC-Derived Microphysiological System

Tatsuya Osaki examines vascular contributions to autism spectrum disorder, focusing on blood–brain barrier integrity and cerebral blood-flow dynamics during early development. Rett syndrome provides a starting point: MeCP2 mutations impair endothelial function, suggesting that vascular cells themselves contribute to disease mechanisms. A three-dimensional microphysiological model built from human induced pluripotent stem cells recreates blood–brain barrier structure and function. Patient-derived endothelial cells form perfusable microvascular networks but show impaired barrier function, a finding independently corroborated in MeCP2-knockout mice. Transcriptomic analyses implicate increased miR-126 expression and disrupted tight junctions; inhibiting miR-126-3p restores barrier function and identifies a potential therapeutic target. The work is extending to hemodynamic changes in other autism subtypes, with two-photon imaging providing in-vivo cross-validation, to identify shared neurovascular mechanisms and candidate interventions.