HPSC-derived mesenchymal stromal cells ameliorate murine autistic-like phenotypes through activating oxytocinergic neurons
10 affiliations
- 1Department of Endocrinology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.
- 2Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou 510080, China.
- 3National-Local Joint Engineering Research Center for Stem Cells and Regenerative Medicine, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
- 4Department of Histoembryology and Cell Biology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
- 5Stem Cells and Regenerative Medicine Joint Laboratory of Sun Yat-sen University and Gaozhou People’s Hospital, Sun Yat-sen University, Guangzhou 510080, China.
- 6Department of Critical Care Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.
- 7Department of Cardiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510120, China.
- 8Jiangxi Provincial Key Laboratory of Cell Precision Therapy, School of Basic Medical Sciences, Jiujiang University, Jiujiang 332005, China.
- 9Department of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou 510630, China.
- 10Guangdong Provincial Key Laboratory of Diabetology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China.
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.
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BibTeX
@article{huang2026hpscderived,
title = {{HPSC-derived mesenchymal stromal cells ameliorate murine autistic-like phenotypes through activating oxytocinergic neurons}},
author = {Yinong Huang and Yixuan Liu and Yilin Liu and Hongjie Liang and Yunli Tong and Ruijie Li and Xiaoran Zhang and Yiling Wang and Yiwen Deng and Jihao Wu and Yue Shu and Qiying Lu and Yuan Qiu and Jinsi Chen and Yucheng Ba and Jiayun Fang and Jiang Hao and Weiqiang Li and Haipeng Xiao and Weijun Huang and Andy Peng Xiang},
journal = {Science Advances},
year = {2026},
month = oct,
doi = {10.1126/sciadv.adt4995},
url = {https://www.science.org/doi/10.1126/sciadv.adt4995},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - HPSC-derived mesenchymal stromal cells ameliorate murine autistic-like phenotypes through activating oxytocinergic neurons
AU - Yinong Huang
AU - Yixuan Liu
AU - Yilin Liu
AU - Hongjie Liang
AU - Yunli Tong
AU - Ruijie Li
AU - Xiaoran Zhang
AU - Yiling Wang
AU - Yiwen Deng
AU - Jihao Wu
AU - Yue Shu
AU - Qiying Lu
AU - Yuan Qiu
AU - Jinsi Chen
AU - Yucheng Ba
AU - Jiayun Fang
AU - Jiang Hao
AU - Weiqiang Li
AU - Haipeng Xiao
AU - Weijun Huang
AU - Andy Peng Xiang
PY - 2026
DA - 2026/10/09
JO - Science Advances
DO - 10.1126/sciadv.adt4995
UR - https://www.science.org/doi/10.1126/sciadv.adt4995
AB - 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.
SN - 2375-2548
ER -