Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2024 Aug 26;15(1):264.
doi: 10.1186/s13287-024-03868-0.

Safety and potential effects of intrathecal injection of allogeneic human umbilical cord mesenchymal stem cell-derived exosomes in complete subacute spinal cord injury: a first-in-human, single-arm, open-label, phase I clinical trial

Mohammadhosein Akhlaghpasand #  1   2 , Roozbeh Tavanaei #  1 , Maede Hosseinpoor  2   3 , Kaveh Oraii Yazdani  4 , Afsane Soleimani  2 , Mojtaba Yousefi Zoshk  5 , Masoud Soleimani  6 , Mohsen Chamanara  7 , Mahdi Ghorbani  1   8 , Mohammad Deylami  9 , Alireza Zali  2 , Reza Heidari  10   11 , Saeed Oraee-Yazdani  12
Affiliations
Clinical Trial

Safety and potential effects of intrathecal injection of allogeneic human umbilical cord mesenchymal stem cell-derived exosomes in complete subacute spinal cord injury: a first-in-human, single-arm, open-label, phase I clinical trial

Mohammadhosein Akhlaghpasand et al. Stem Cell Res Ther. .

Abstract

Objective: Neurological and functional impairments are commonly observed in individuals with spinal cord injury (SCI) due to insufficient regeneration of damaged axons. Exosomes play a crucial role in the paracrine effects of mesenchymal stem cells (MSCs) and have emerged as a promising therapeutic approach for SCI. Thus, this study aimed to evaluate the safety and potential effects of intrathecal administration of allogeneic exosomes derived from human umbilical cord MSCs (HUC-MSCs) in patients with complete subacute SCI.

Methods: This study was a single-arm, open-label, phase I clinical trial with a 12-month follow-up period. HUC-MSCs were extracted from human umbilical cord tissue, and exosomes were isolated via ultracentrifugation. After intrathecal injection, each participant a underwent complete evaluation, including neurological assessment using the American Spinal Injury Association (ASIA) scale, functional assessment using the Spinal Cord Independence Measure (SCIM-III), neurogenic bowel dysfunction (NBD) assessment using the NBD score, modified Ashworth scale (MAS), and lower urinary tract function questionnaire.

Results: Nine patients with complete subacute SCI were recruited. The intrathecal injection of allogeneic HUC-MSCs-exosomes was safe and well tolerated. No early or late adverse event (AE) attributable to the study intervention was observed. Significant improvements in ASIA pinprick (P-value = 0.039) and light touch (P-value = 0.038) scores, SCIM III total score (P-value = 0.027), and NBD score (P-value = 0.042) were also observed at 12-month after the injection compared with baseline.

Conclusions: This study demonstrated that intrathecal administration of allogeneic HUC-MSCs-exosomes is safe in patients with subacute SCI. Moreover, it seems that this therapy might be associated with potential clinical and functional improvements in these patients. In this regard, future larger phase II/III clinical trials with adequate power are highly required.

Trial registration: Iranian Registry of Clinical Trials, IRCT20200502047277N1. Registered 2 October 2020, https://en.irct.ir/trial/48765 .

Keywords: Exosomes; Mesenchymal stem cells; Neuroprotection; Spinal cord injury.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no competing interests .

Figures

Fig. 1
Fig. 1
(A) Flow cytometric analysis revealed positive expression of CD29, CD73, CD90, and CD105, while indicating negative expression for CD34 and CD 45 markers in HUC-MSCs. (B) The size distribution of exosomes was determined through dynamic light scattering analysis; Mean 63.2 nm, SD: 15.2 nm. (C) Transmission electron microscopy images illustrate the structural features of exosomes. (D) Western blot analysis indicated the expression of exosomal surface markers, including CD9 and CD81 (additional file 1: uncropped blots)
Fig. 2
Fig. 2
Consolidated Standards of Reporting Trials (CONSORT) 2010 flow diagram
Fig. 3
Fig. 3
Neurological, functional, and neurogenic bowel dysfunction (NBD) changes in the patients over the study period (A-H). Changes of ASIA motor, pinprick, light touch, spinal cord independence measure (SCIM) version III total, self-care, respiration and sphincter management, mobility, and NBD scores in patients at baseline, 6-, and 12-month after the intrathecal injection
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. David G, Mohammadi S, Martin AR, Cohen-Adad J, Weiskopf N, Thompson A, Freund P. Traumatic and nontraumatic spinal cord injury: pathological insights from neuroimaging. Nat Reviews Neurol. 2019;15(12):718–31.10.1038/s41582-019-0270-5 - DOI - PubMed
    1. James SL, Theadom A, Ellenbogen RG, Bannick MS, Montjoy-Venning W, Lucchesi LR, et al. Global, regional, and national burden of traumatic brain injury and spinal cord injury, 1990–2016: a systematic analysis for the global burden of Disease Study 2016. Lancet Neurol. 2019;18(1):56–87. 10.1016/S1474-4422(18)30415-0 - DOI - PMC - PubMed
    1. Ahuja CS, Wilson JR, Nori S, Kotter M, Druschel C, Curt A, Fehlings MG. Traumatic spinal cord injury. Nat Reviews Disease Primers. 2017;3(1):1–21. - PubMed
    1. Hayta E, Elden H. Acute spinal cord injury: a review of pathophysiology and potential of non-steroidal anti-inflammatory drugs for pharmacological intervention. J Chem Neuroanat. 2018;87:25–31. 10.1016/j.jchemneu.2017.08.001 - DOI - PubMed
    1. Bradbury EJ, Burnside ER. Moving beyond the glial scar for spinal cord repair. Nat Commun. 2019;10(1):3879. 10.1038/s41467-019-11707-7 - DOI - PMC - PubMed

Publication types