ArticleCell death & disease2026
Extracellular vesicles from stem cells rescue cellular phenotypes and behavioral deficits in SHANK3-associated ASD neuronal and mouse models.
Article in Cell death & disease, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
4 citing papers in PubMed.
- Astrocyte-Derived Extracellular Vesicles and the Evolution of Neural Complexity: Perspectives on Vesicle-Mediated Neuron-Glia Communication.Molecular neurobiology · 2026Review
- Review
- Extracellular Vesicles in Angelman Syndrome: Expanding UBE3A Role beyond a Cell Autonomous Mechanism.Journal of experimental neurology · 2026Article
- A phenotype- and potency-gated extracellular vesicle allocation hypothesis for autism.Frontiers in child and adolescent psychiatry · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors.
Funding
Abstract
Extracellular vesicles (EVs) are lipid bilayer-enclosed structures that mediate intercellular communication by transferring diverse cargoes, including RNA and proteins. SHANK3, a synaptic scaffolding protein critical for synapse structure and function, is implicated in autism spectrum disorder (ASD) and Phelan-McDermid Syndrome (PMS). Early hyperexcitability in cortical neurons is a characterized endophenotype in ASD. Here, we investigated EV-mediated effects in the context of SHANK3 deficiency using human iPSC-derived cortical neurons and Shank3B-/- mice. Switching EVs between SHANK3 mutant and control neurons revealed that SHANK3 mutant-derived EVs transferred the hyperexcitability and accelerated maturation phenotypes to control neurons. Proteomic analysis revealed enrichment of synaptic structural regulators (e.g., ACTB, CFL1, AGRN, and CLSTN1) in SHANK3 mutant neuron-derived EVs. This is consistent with known actin cytoskeletal dysregulation driven by SHANK3 deficiency. However, control neuron-derived EVs failed to rescue mutant phenotypes, likely due to their decreased enrichment of synaptic proteins and related pathways. Further, EVs from mesenchymal stem cells (MSCs) and healthy donor iPSCs, containing synaptic modulators such as complement proteins (C1R, C1S), plasticity-associated proteins (MDK, IGFBP3), and homeostatic regulators (FGF2, SFRP1), rescued the hyperexcitability and normalized the maturation in SHANK3 mutant neurons. In addition, intranasal administration of iPSC-derived EVs in Shank3B-/- mice significantly rescued ASD-like behavioral deficits, emphasizing their therapeutic potential. Together, these findings reveal a novel EV-mediated mechanism for modulating dysregulated excitability and synaptic maturation, addressing a critical unmet need in ASD and associated neurodevelopmental disorders.
Indexed as
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.