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Adv."],"published-print":{"date-parts":[[2026,10,9]]},"abstract":"<jats:p>\n                    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)\u2013derived MSCs alleviate anxiety, grooming, and social impairments in\n                    <jats:italic toggle=\"yes\">Shank3B<\/jats:italic>\n                    knockout mice, a monogenic ASD model. Intravenously infused MSCs localize to the neurohypophysis, interface with oxytocin (OT)\u2013producing neuron axons, and activate OT\n                    <jats:sup>+<\/jats:sup>\n                    neurons in the paraventricular nucleus (PVN). MSC treatment also reduces autistic-like phenotypes in BTBR T +\n                    <jats:italic toggle=\"yes\">Itpr3tf<\/jats:italic>\n                    \/J mice, a model of idiopathic ASD, in an OT\n                    <jats:sup>+<\/jats:sup>\n                    neuron\u2013dependent manner. Mechanistically, prostaglandin E2 (PGE2) secreted by MSCs instigates the activation of OT\n                    <jats:sup>+<\/jats:sup>\n                    neuron, while suppression of PGE2 production via short hairpin RNA (shRNA)\u2013mediated knockdown of\n                    <jats:italic toggle=\"yes\">PTGS1<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">PTGES<\/jats:italic>\n                    diminishes their therapeutic efficacy. These findings reveal a mechanism whereby MSCs modulate OT\n                    <jats:sup>+<\/jats:sup>\n                    neuroendocrine circuits to improve ASD-related behaviors.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.adt4995","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T18:06:59Z","timestamp":1791569219000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["HPSC-derived mesenchymal stromal cells ameliorate murine autistic-like phenotypes through activating oxytocinergic neurons"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7364-2894","authenticated-orcid":true,"given":"Yinong","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Endocrinology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China."},{"name":"Center 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."},{"name":"National-Local Joint Engineering Research Center for Stem Cells and Regenerative Medicine, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China."},{"name":"Department of Histoembryology and Cell Biology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0572-7164","authenticated-orcid":true,"given":"Yixuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Center 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."},{"name":"National-Local Joint Engineering Research Center for Stem Cells and Regenerative Medicine, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China."},{"name":"Stem Cells and Regenerative Medicine Joint Laboratory of Sun Yat-sen University and Gaozhou People\u2019s Hospital, Sun Yat-sen University, Guangzhou 510080, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5693-3594","authenticated-orcid":true,"given":"Yilin","family":"Liu","sequence":"additional","affiliation":[{"name":"Center 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."},{"name":"National-Local Joint Engineering Research Center for Stem Cells and Regenerative Medicine, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China."},{"name":"Department of Critical Care Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0542-4455","authenticated-orcid":true,"given":"Hongjie","family":"Liang","sequence":"additional","affiliation":[{"name":"Center 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."},{"name":"National-Local Joint Engineering Research Center for Stem Cells and Regenerative Medicine, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China."},{"name":"Stem Cells and Regenerative Medicine Joint Laboratory of Sun Yat-sen University and Gaozhou People\u2019s Hospital, Sun Yat-sen University, Guangzhou 510080, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3743-3403","authenticated-orcid":true,"given":"Yunli","family":"Tong","sequence":"additional","affiliation":[{"name":"Center for Stem Cell 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