Authors
Yinong Huang, Yixuan Liu, Yilin Liu, Hongjie Liang, Yunli Tong, Ruijie Li, Xiaoran Zhang, Yiling Wang, Yiwen Deng, Jihao Wu, Yue Shu, Qiying Lu, Yuan Qiu, Jinsi Chen, Yucheng Ba, Jiayun Fang, Jiang Hao, Weiqiang Li, Haipeng Xiao, Weijun Huang, Andy Peng Xiang
Published in
Science advances. Volume 12. Issue 41. Pages eadt4995. Oct 09, 2026. Epub Oct 09, 2026.
Abstract
Autism spectrum disorder (ASD) is a heritable neurodevelopmental disorder marked by social deficits, repetitive behaviors, and psychiatric comorbidities. Despite its rising global prevalence, effective treatments remain elusive. Mesenchymal stromal cells (MSCs) offer therapeutic promise for ASD, although their mechanisms are unclear. Here, we show that induced pluripotent stem cell (iPSC)-derived MSCs alleviate anxiety, grooming, and social impairments in Shank3B knockout mice, a monogenic ASD model. Intravenously infused MSCs localize to the neurohypophysis, interface with oxytocin (OT)-producing neuron axons, and activate OT+ neurons in the paraventricular nucleus (PVN). MSC treatment also reduces autistic-like phenotypes in BTBR T + Itpr3tf/J mice, a model of idiopathic ASD, in an OT+ neuron-dependent manner. Mechanistically, prostaglandin E2 (PGE2) secreted by MSCs instigates the activation of OT+ neuron, while suppression of PGE2 production via short hairpin RNA (shRNA)-mediated knockdown of PTGS1 and PTGES diminishes their therapeutic efficacy. These findings reveal a mechanism whereby MSCs modulate OT+ neuroendocrine circuits to improve ASD-related behaviors.
PMID:
42853941
Bibliographic data and abstract were imported from PubMed on 10 Oct 2026.
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