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©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
Multiroute administration of Wharton’s jelly mesenchymal stem cells in chronic complete spinal cord injury: A phase I safety and feasibility study
Necati Kaplan, Serdar Kabatas, Erdinç Civelek, Eyüp Can Savrunlu, Tolga Akkoc, Osman Boyalı, Erek Öztürk, Halil Can, Ali Genc, Erdal Karaöz
Necati Kaplan, Department of Neurosurgery, Istanbul Rumeli University, Çorlu Reyap Hospital, Tekirdağ 59860, Türkiye
Serdar Kabatas, Erdinç Civelek, Osman Boyalı, Department of Neurosurgery, University of Health Sciences Türkiye, Gaziosmanpaşa Training and Research Hospital, Istanbul 34255, Türkiye
Serdar Kabatas, Center for Stem Cell & Gene Therapy Research and Practice, University of Health Sciences Türkiye, İstanbul 34255, Türkiye
Eyüp Can Savrunlu, Department of Neurosurgery, Versa Hospital, Nevşehir 50300, Türkiye
Tolga Akkoc, Tubitak Marmara Research Center, Genetic Engineering and Biotechnology Institute, Kocaeli 41470, Türkiye
Erek Öztürk, Department of Neurosurgery, Orthopaediezentrum Magdeburg, Magdeburg 39112, Saxony-Anhalt, Germany
Halil Can, Department of Neurosurgery, Atlas University, İstanbul 34408, Türkiye
Ali Genc, Department of Neurosurgery, Palmiye Hospital, Hatay 31200, Türkiye
Erdal Karaöz, Center for Regenerative Medicine and Stem Cell Research & Manufacturing, Liv Hospital, Istanbul 34340, Türkiye
Erdal Karaöz, Department of Histology and Embryology, Istinye University, Faculty of Medicine, Zeytinburnu 34010, Istanbul, Türkiye
Erdal Karaöz, Istinye University, Center for Stem Cell and Tissue Engineering Research and Practice, Beşiktaş 34340, Istanbul, Türkiye
Author contributions: Kaplan N, Kabatas S, and Karaöz E contributed to the concept of this manuscript; Kaplan N, Kabatas S, Savrunlu EC, and Karaöz E designed the manuscript; Kabatas S, Civelek E, Akkoc T, and Karaöz E participated in the supervision of this manuscript; Kaplan N, Kabatas S, Civelek E, Savrunlu EC, Boyalı O, Öztürk E, Can H, and Genc A contributed to the analysis and/or interpretation of data; Kabatas S, Civelek E, Savrunlu EC, Boyalı O, Öztürk E, Can H, Genc A, and Karaöz E searched the literature; Kaplan N, Kabatas S, Savrunlu EC, Akkoc T, Boyalı O, and Öztürk E wrote the manuscript; Kabatas S, Civelek E, Savrunlu EC, Akkoc T, and Karaöz E contributed to the critical review of this manuscript.
Institutional review board statement: Ethical approval to report this study was obtained from the institutional review board of Turkish Ministry of Health, Department of Organ, Tissue Transplant and Dialysis Services’ Scientific Committee, Ankara, Türkiye, No. 56733164-203-E.2659.
Clinical trial registration statement: The MSC trial was approved by the Turkish Ministry of Health.
Informed consent statement: There are human subjects in this article, and written informed consents were obtained from the patient for their anonymized information to be published in this article and before the stem cell therapies.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
CONSORT 2010 statement: The authors have read the CONSORT 2010 Statement, and the manuscript was prepared and revised according to the CONSORT 2010 Statement.
Data sharing statement: No additional data are available.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Serdar Kabatas, MD, Full Professor, Department of Neurosurgery, University of Health Sciences Türkiye, Gaziosmanpaşa Training and Research Hospital, Karayolları Mahallesi, Osmanbey Caddesi 616. Sokak No. 10, Gaziosmanpaşa, Istanbul 34255, Türkiye.
kabatasserdar@hotmail.com
Received: September 26, 2024
Revised: January 9, 2025
Accepted: March 27, 2025
Published online: May 26, 2025
Processing time: 241 Days and 22 Hours
BACKGROUND
Traumatic spinal cord injury (SCI) is a life-altering condition that results in long-term complications, including progressive neurodegeneration and cord atrophy. It presents a significant unmet medical need with extensive social and economic burdens.
AIM
To evaluate the safety and preliminary efficacy of allogeneic mesenchymal stem cells derived from Wharton’s jelly (WJ-MSCs) in patients with chronic complete SCI. The primary objective was to assess whether WJ-MSCs could facilitate neurological recovery and improve the quality of life in this patient population.
METHODS
This open-label, multicenter phase I study investigated the effects of administering WJ-MSCs via three delivery routes: Intrathecal (for localized spinal targeting); intramuscular (for targeting end organ); and intravenous (for systemic immunomodulation). While all three routes were used concurrently to enhance therapeutic synergy, neurological, sensory, and functional scales were used to assess overall efficacy. Participants with chronic SCI (duration of at least 6 months) who had significant impairment and disability were eligible for inclusion. WJ-MSCs were administered twice monthly for 2 months, with each route receiving a dose of 1 × 106 cells/kg. Patients were closely monitored for 1 year following treatment.
RESULTS
At baseline, participants displayed considerable functional deficits, as indicated by the following scores: Functional independence measure of 77.5 ± 2.26; Modified Ashworth Scale of 15.83 ± 4.83; American Spinal Injury Association (ASIA) Motor score of 1.67 ± 2.66; ASIA Light Touch and Pin-Prick scores of 62 ± 18.42 each; Wexner Incontinence Score of 20; and Qualiveen Short Form, a validated questionnaire specifically designed to assess the impact of urinary dysfunction on quality of life in individuals with SCI, score of 32. Following WJ-MSC therapy, significant improvements were observed in all neurological functions over the 1-year follow-up. Notably, the ASIA Motor score improved significantly (χ2 = 23.938, P < 0.001), and Qualiveen Short Form scores demonstrated a substantial enhancement in quality of life (z = -2.214, P < 0.05).
CONCLUSION
This phase I study, conducted without a control group, suggests that the administration of WJ-MSCs through multiple routes is both safe and potentially effective in patients with chronic complete SCI. However, the observed neurological improvements cannot be solely attributed to WJ-MSC therapy, as concurrent pharmacological and rehabilitative interventions were not controlled. These findings indicated that WJ-MSC therapy may offer a promising approach for enhancing neurological function and quality of life in this challenging patient population. Further research with larger cohorts and extended follow-up is necessary to validate these preliminary results.
Core Tip: Spinal cord injury causes severe disability with significant impairments in sensory and motor functions and dysfunction in multiple organs. We investigated the therapeutic potential of Wharton’s jelly-derived mesenchymal stem cells administered through a triple-route delivery system (intrathecal, intramuscular, and intravenous). The treatment resulted in significant improvements in motor and sensory functions. Patients experienced an improved quality of life. The procedure was well-tolerated with no significant side effects or safety concerns. No adverse events were reported highlighting the potential of Wharton's jelly-derived mesenchymal stem cell therapy as a safe and effective treatment option for individuals with chronic spinal cord injury.
