Abstract
Current treatments for neuromyelitis optica spectrum disorder (NMOSD) highlight recurrence management, while little attention is paid to the relief of residual neurological dysfunction. Here we aimed to evaluate the safety and efficacy of human umbilical cord-derived mesenchymal stromal cells (hUC-MSCs) in reducing relapses and mitigating neurological impairments. This trial, hUC-MSC-NMOSD (ChiCTR-INR-16008037), a single-arm, dose-escalation, open-label study, included 31 NMOSD patients of three dose groups received four infusions every three months, with 15-month follow-up. Primary outcome was time to first recurrence; secondary outcomes focused on clinical scores, MRI lesions and exploratory findings. HUC-MSC infusion was well tolerated in all groups of patients. Adverse events were mostly mild, with urinary tract infections being the most common. Severe adverse events were rare and unrelated to the treatment. The median relapse-free interval increased significantly post-treatment from 305 (95%CI 226-382·5) to 760 (589-1016·5) (p < 0·001), especially in the medium- and high-dose groups. During the two years before and after therapy, the mean Annualized Relapse Rate (ARR) dropped considerably from 1 (0·75-1) to 0 (0-0·5) (p < 0·001). Clinical scores improved in the low and medium-dose groups. The total volume of high-signal white matter lesions in brain significantly decreased after therapy from 4144·5 (2857·2-5508·6) to 2914·4 (2453-3684·11) (p = 0·016). Exploratory single-cell RNA sequencing and metabolomics detection revealed a potential participation of thioredoxin and oxidative phosphorylation (OXPHOS)-mediated boosting of Treg differentiation and suppressive capacity. This trial indicates that intravenous hUC-MSC administration is safe and shows potential efficacy in treating NMOSD. Medium dose might be the best possible compromise between safety and effectiveness.
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Data availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
Code availability
ScRNA-sequencing data have been deposited to National Center for Biotechnology Information (NCBI) under the BioProject number PRJNA1402125. All data reported in our research will be shared by the lead contact upon request. Our research does not report original code. Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.
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Acknowledgements
We would like to thank all the staff and patients involved with the study. We would like to acknowledge the role of the Clinical Research Centre, Ren Ji Hospital, in supporting the ongoing delivery of the trial at the sites. We are grateful to all the staff of the Clinical Research Center of School of Medicine, Shanghai Jiao Tong University for their support in designing the present study protocol. This study was funded by National Natural Science Foundation of China (82071341, 72204161); New Quality Clinical Specialty Program of High-end Medical Disciplinary Construction in Shanghai Pudong New Area (2024-PWXZ-16); The Investigator-initiated Trial Program of Shanghai Pudong New Area Health Commission (the Medical and Industrial Integration Program, 2025-PWYC-06); Interdisciplinary Program of Shanghai Jiao Tong University (YG2023LC04); The Municipal Commission of Health and Family Planning Foundation of Shanghai Pudong New Area (PW2022E-01).
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X.Y.Y. designed the clinical trial, recruited the subjects and wrote the manuscript. Y.T.G. and B.Y.Q. conceptualized the study, provided administrative support and approved the design. H.J.Y. helped prepare hUC-MSCs, quality control and final application, designed and helped carry out the experiments, conducted and interpreted the statistical and bioinformatics analysis, revised the manuscript. X.Y.Y., Z.J.L., and N.Z. were responsible for clinical trial treatment procedure. L.X. provided statistical support. C.R.X. and Y.S.W. carried out patients’ follow-up visit and ensured data quality. X.Z.P. helped collect the clinical data and carried out the in vitro experiments. M.Z.Z., X.Y.W., and Y.C. collected the clinical data. Y.Z.(MD), WB.W., Y.L., and Y.D. helped conduct the treatment and administrative procedure. H.Z., LF.L., H.M.X. were responsible for hUC-MSCs’ quality and decided the dosage. J.D., YF.W., Z.W., YY.S., and K.W. helped recruit the patients and follow-up visit. H.Y.Q., Y.Z.(BS), Y.Y.J., L.P.N., J.L.Y., Q.G., J.H.X., and Y.F.M. provided hospitalization support for subjects. All authors approved the above contribution and the final version of manuscript.
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Yao, XY., Lu, ZJ., Zhao, N. et al. Human umbilical cord mesenchymal stromal cells therapy for neuromyelitis optica spectrum disorder: a phase 1/2a trial. Cell Death Differ (2026). https://doi.org/10.1038/s41418-026-01720-x
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DOI: https://doi.org/10.1038/s41418-026-01720-x
