Oxytocin · research summary

HPSC-derived mesenchymal stromal cells ameliorate murine autistic-like phenotypes through activating oxytocinergic neurons.

Science advances · 2026. Summary drawn from the study's full text. Each statement is followed by the exact sentence it comes from. This is a research summary, not medical advice.

Study type

Preclinical study using murine models of autism spectrum disorder
“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.”

Subjects

Male Shank3B knockout mice and BTBR T + Itpr3tf/J mice
“Since female mice exhibit periodic fluctuations in sex hormones during the estrous cycle, which have been shown to substantially influence OT levels (36, 37) as well as social behavior patterns (38), we exclusively used male mice for all behavioral experiments.”

Sample size

Varied by experiment, with group sizes ranging from n=3 to n=17
“WT, n = 14; Shank3B KO + PBS, n = 17; Shank3B KO + MSC, n = 15.”

Duration

Treatments administered at 3 and 7 weeks of age with assessments up to 28 days post-treatment
“Following MSC administration, circulating OT levels exhibited a substantial increase as early as 1 day after treatment and remained elevated for at least 28 days posttransplantation (Fig. 4B).”

Reported findings

MSC therapy alleviated anxiety, grooming, and social impairments in Shank3B knockout mice
“MSC therapy substantially alleviates autistic-like phenotypes in Shank3B knockout mice.”
Intravenously infused MSCs localized to the neurohypophysis and activated oxytocin-producing neurons
“Intravenously infused MSCs localize to the neurohypophysis, interface with oxytocin (OT)–producing neuron axons, and activate OT+ neurons in the paraventricular nucleus (PVN).”
Prostaglandin E2 secreted by MSCs was identified as a mediator for OT neuron activation
“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.”

Limitations stated by the authors

Study was conducted exclusively in male mice and used preclinical models, limiting generalizability to clinical populations
“All behavioral and mechanistic data in the current study were acquired exclusively from male mice, excluding potential sex-dependent variability in OT circuit function and MSC treatment responsiveness.”

Source: PubMed 42853941 · DOI 10.1126/sciadv.adt4995 · all study summaries

Subjects

Male Shank3B knockout mice and BTBR T + Itpr3tf/J mice

“Since female mice exhibit periodic fluctuations in sex hormones during the estrous cycle, which have been shown to substantially influence OT levels (36, 37) as well as social behavior patterns (38), we exclusively used male mice for all behavioral experiments.”

Reported findings

MSC therapy alleviated anxiety, grooming, and social impairments in Shank3B knockout mice

“MSC therapy substantially alleviates autistic-like phenotypes in Shank3B knockout mice.”

Intravenously infused MSCs localized to the neurohypophysis and activated oxytocin-producing neurons

“Intravenously infused MSCs localize to the neurohypophysis, interface with oxytocin (OT)–producing neuron axons, and activate OT+ neurons in the paraventricular nucleus (PVN).”

Prostaglandin E2 secreted by MSCs was identified as a mediator for OT neuron activation

“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.”

Limitations stated by the authors

Study was conducted exclusively in male mice and used preclinical models, limiting generalizability to clinical populations

“All behavioral and mechanistic data in the current study were acquired exclusively from male mice, excluding potential sex-dependent variability in OT circuit function and MSC treatment responsiveness.”