Three repeated intrathecal injections of allogenic umbilical cord-derived mesenchymal stromal cells in autism spectrum disorder: a Phase I clinical trial.
12 affiliations
- 1R&D Department, Royan Stem Cell Technology Company, Tehran, Iran.
- 2Psychiatric Research Center, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, Iran.
- 3Division of Pediatric Intensive Care Unit, Children's Medical Center, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran.
- 4Department of Radiology, Children's Medical Center, Tehran University of Medical Science, Tehran, Iran.
- 5Advanced Diagnostic and Interventional Radiology Research Center, Tehran University of Medical Sciences, Tehran, Iran.
- 6Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
- 7Department of Pediatric Hematology and Oncology, Dr Sheikh Pediatric Hospital, Mashhad University of Medical Sciences, Mashhad, Iran.
- 8Department of Pediatrics, Division of Pediatric Neurology, Children's Medical Center, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran.
- 9Pediatric Cell and Gene Therapy Research Center, Gene, Cell & Tissue Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
- 10Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran. [email protected].
- 11Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran. [email protected].
- 12Psychiatric Research Center, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, Iran. [email protected].
Abstract
Background: Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition of etiology, characterized by deficits in social communication and restricted, repetitive behaviors. Despite its growing prevalence, no treatment has yet demonstrated consistent efficacy across the full spectrum of ASD phenotypes. This Phase I, open-label study investigates the safety and feasibility of three repeated intrathecal injections of allogeneic Umbilical Cord Tissue–Derived Mesenchymal Stromal Cells (UC-MSCs) in children diagnosed with ASD.
Methods: Five children (aged 3-7) with ASD, confirmed by Diagnostic and Statistical Manual of Mental Disorders- Fifth Edition (DSM-5) criteria and on stable behavioral and pharmacologic regimens for at least two months, received three intrathecal (IT) injections of 20 × 10⁶ UC-MSCs at one-month intervals. Safety was monitored over six months based on Common Terminology Criteria for Adverse Events (CTCAE). Preliminary behavioral assessments, including the Childhood Autism Rating Scale (CARS), Autism Treatment Evaluation Checklist (ATEC), and the Behavior Problem Inventory (BPI-S), were conducted at the baseline, one-, two-, four-, and six-month follow-ups. Cerebrospinal fluid (CSF) cytokine profiles were measured prior to each injection. Electroencephalography (EEG) and Diffusion Tensor Imaging (DTI) were performed at baseline and the final follow-up.
Results: The treatment was safe and well-tolerated with no serious adverse events (SAEs). All participants experienced at least one mild to moderate, transient adverse event (AEs), most commonly fever (5/5) and nausea (4/5). Exploratory behavioral improvements were observed in CARS in all children, while two participants moved from the mild-to-moderate to the non-autistic ranges, and three shifted from the severe to the mild-to-moderate range. Other measures also improved, though the persistence of these improvements was varied. CSF cytokines showed consistent reduction, particularly in TNF-\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}α\end{document} and IL-6 levels across participants, confirming the immunomodulatory impact of UC-MSC administration. The EEG findings revealed that the spectral pattern shifted toward a more typical profile in one participant after treatment.
Conclusions: This Phase I study showed that three repeated IT injections of UC-MSCs are safe and well-tolerated in children with ASD. Preliminary behavioral and biomarker improvements warrant further study in larger controlled trials.
Trial registration: Trial Registration ID: IRCT20200217046526N3.
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s13287-026-05122-1.
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BibTeX
@article{khodadoust2026three,
title = {{Three repeated intrathecal injections of allogenic umbilical cord-derived mesenchymal stromal cells in autism spectrum disorder: a Phase I clinical trial.}},
author = {Elaheh Khodadoust and Hadi Zarafshan and Masoumeh Nouri and Anahita Majmaa and Ali Khaleghi and Fatemeh Zamani and Milad Seyfi and Mohammad Amin Shahrbaf and Solaleh Samimi and Bahareh Sadri and Seyedeh Malihe Mahmoodi and Norouz Abdi and Ali Ghasemi and Mahmoud Reza Ashrafi and Morteza Zarrabi and Massoud Vosough and Mohammad Reza Mohammadi},
journal = {Stem cell research \& therapy},
year = {2026},
month = jul,
doi = {10.1186/s13287-026-05122-1},
url = {https://europepmc.org/article/MED/42958455},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Three repeated intrathecal injections of allogenic umbilical cord-derived mesenchymal stromal cells in autism spectrum disorder: a Phase I clinical trial.
AU - Elaheh Khodadoust
AU - Hadi Zarafshan
AU - Masoumeh Nouri
AU - Anahita Majmaa
AU - Ali Khaleghi
AU - Fatemeh Zamani
AU - Milad Seyfi
AU - Mohammad Amin Shahrbaf
AU - Solaleh Samimi
AU - Bahareh Sadri
AU - Seyedeh Malihe Mahmoodi
AU - Norouz Abdi
AU - Ali Ghasemi
AU - Mahmoud Reza Ashrafi
AU - Morteza Zarrabi
AU - Massoud Vosough
AU - Mohammad Reza Mohammadi
PY - 2026
DA - 2026/07/30
JO - Stem cell research & therapy
DO - 10.1186/s13287-026-05122-1
UR - https://europepmc.org/article/MED/42958455
AB - Background: Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition of etiology, characterized by deficits in social communication and restricted, repetitive behaviors. Despite its growing prevalence, no treatment has yet demonstrated consistent efficacy across the full spectrum of ASD phenotypes. This Phase I, open-label study investigates the safety and feasibility of three repeated intrathecal injections of allogeneic Umbilical Cord Tissue–Derived Mesenchymal Stromal Cells (UC-MSCs) in children diagnosed with ASD. Methods: Five children (aged 3-7) with ASD, confirmed by Diagnostic and Statistical Manual of Mental Disorders- Fifth Edition (DSM-5) criteria and on stable behavioral and pharmacologic regimens for at least two months, received three intrathecal (IT) injections of 20 × 10⁶ UC-MSCs at one-month intervals. Safety was monitored over six months based on Common Terminology Criteria for Adverse Events (CTCAE). Preliminary behavioral assessments, including the Childhood Autism Rating Scale (CARS), Autism Treatment Evaluation Checklist (ATEC), and the Behavior Problem Inventory (BPI-S), were conducted at the baseline, one-, two-, four-, and six-month follow-ups. Cerebrospinal fluid (CSF) cytokine profiles were measured prior to each injection. Electroencephalography (EEG) and Diffusion Tensor Imaging (DTI) were performed at baseline and the final follow-up. Results: The treatment was safe and well-tolerated with no serious adverse events (SAEs). All participants experienced at least one mild to moderate, transient adverse event (AEs), most commonly fever (5/5) and nausea (4/5). Exploratory behavioral improvements were observed in CARS in all children, while two participants moved from the mild-to-moderate to the non-autistic ranges, and three shifted from the severe to the mild-to-moderate range. Other measures also improved, though the persistence of these improvements was varied. CSF cytokines showed consistent reduction, particularly in TNF-\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}α\end{document} and IL-6 levels across participants, confirming the immunomodulatory impact of UC-MSC administration. The EEG findings revealed that the spectral pattern shifted toward a more typical profile in one participant after treatment. Conclusions: This Phase I study showed that three repeated IT injections of UC-MSCs are safe and well-tolerated in children with ASD. Preliminary behavioral and biomarker improvements warrant further study in larger controlled trials. Trial registration: Trial Registration ID: IRCT20200217046526N3. Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s13287-026-05122-1.
SN - 1757-6512
ER -