Sensory abnormalities in autism spectrum disorder and their in vitro modeling.

This research review suggests that many autism symptoms might be connected to problems with how the brain processes touch and body sensations. The authors think an imbalance in brain activity (too much excitation, not enough inhibition) causes sensory issues that then lead to social and behavioral difficulties. They discuss new laboratory models using human stem cells to better understand these problems and find potential treatments.

This review proposes that sensory abnormalities in autism spectrum disorder may stem from somatosensory system dysfunction caused by excitatory-inhibitory (E/I) imbalance in the brain. The authors suggest this imbalance could drive sensory impairments that contribute to core social and behavioral deficits in autism. The review examines how human induced pluripotent stem cell (hiPSC)-derived assembloid models can be used to study these mechanisms, while critically evaluating their limitations including cellular immaturity and absence of key non-neuronal components. Advanced approaches like co-culture systems, xenotransplantation, and bioengineering are discussed as potential solutions to overcome current model limitations.

This work is primarily theoretical and laboratory-focused. While it may inform future research directions and potentially lead to new therapeutic targets, direct clinical applications are not yet available. The review highlights promising research tools that may eventually contribute to better understanding and treatment of sensory issues in autism.

This is a theoretical review rather than empirical research. The proposed mechanisms are not directly tested. Current assembloid models have significant limitations that may not fully represent human autism pathophysiology.

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.