Sensory abnormalities in autism spectrum disorder and their in vitro modeling

Abstract

Autism Spectrum Disorder (ASD) is characterized by deficits in social interaction, alongside abnormal sensory reactivity that often manifests as avoidance or repetitive behaviors. This review proposes that these core features may stem from somatosensory system dysfunction responsible for processing sensory information driven by an underlying excitatory-inhibitory (E/I) imbalance, a common finding in ASD models, which could drive such sensory impairments and ultimately contribute to the core social and behavioral deficits. We explore how recent advancements in hiPSC-derived assembloid models, which integrate multiple components of the human somatosensory pathway, provide a powerful platform to investigate these mechanisms. Crucially, this review not only highlights the promise of these models but also provides a critical evaluation of their inherent limitations, including cellular immaturity and the absence of key non-neuronal components. By examining the ongoing strategies to overcome these challenges, such as advanced co-culture systems, xenotransplantation, and bioengineering, this review offers a comprehensive outlook on the future of assembloid technology in elucidating ASD pathophysiology and developing novel therapeutic strategies.