Clinical Trials Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Jan 26, 2024; 16(1): 19-32
Published online Jan 26, 2024. doi: 10.4252/wjsc.v16.i1.19
Effects of exosomes from mesenchymal stem cells on functional recovery of a patient with total radial nerve injury: A pilot study
Erdinç Civelek, Serdar Kabatas, Eyüp Can Savrunlu, Furkan Diren, Necati Kaplan, Demet Ofluoğlu, Erdal Karaöz
Erdinç Civelek, Department of Neurosurgery, University of Health Sciences, Gaziosmanpaşa Training and Research Hospital, Gaziosmanpaşa 34255, Istanbul, Turkey
Serdar Kabatas, Furkan Diren, Department of Neurosurgery, University of Health Sciences Turkey, Gaziosmanpaşa Training and Research Hospital, Gaziosmanpaşa 34255, Istanbul, Turkey
Serdar Kabatas, Center for Stem Cell & Gene Therapy Research and Practice, University of Health Sciences Turkey, Gaziosmanpaşa 34255, Istanbul, Turkey
Eyüp Can Savrunlu, Department of Neurosurgery, Nevşehir State Hospital, Nevşehir 50300, Turkey
Necati Kaplan, Department of Neurosurgery, Istanbul Rumeli University, Çorlu Reyap Hospital, Çorlu 59860, Tekirdağ, Turkey
Demet Ofluoğlu, Department of Physical Medicine and Rehabilitation, Ofluoğlu Klinik, Göztepe 34728, Istanbul, Turkey
Erdal Karaöz, Liv Hospital, Center for Regenerative Medicine and Stem Cell Research & Manufacturing (LivMedCell), Beşiktaş 34340, Istanbul, Turkey
Erdal Karaöz, Department of Histology and Embryology, Istinye University, Faculty of Medicine, Zeytinburnu 34010, Istanbul, Turkey
Erdal Karaöz, Istinye University, Center for Stem Cell and Tissue Engineering Research and Practice, Beşiktaş 34340, Istanbul, Turkey
Author contributions: Civelek E, Kabatas S, and Karaöz E concepted this study and contributed to the supervision of this article; Civelek E, Kabatas S, Savrunlu EC, and Diren F designed this study; Civelek E, Kabatas S, Savrunlu EC, Diren F, Kaplan N, and Ofluoğlu D participated in the analysis and/or interpretation of this manuscript; Civelek E, Kabatas S, Savrunlu EC, Diren F, and Ofluoğlu D took part in the literature search; Civelek E, Kabatas S, Savrunlu EC, Diren F, and Karaöz E wrote the manuscript; Civelek E, Kabatas S, Savrunlu EC, and Ofluoğlu D contributed to the critical reviews of this article.
Institutional review board statement: The present study was approved by the medical ethics committee of the authors’ institution (protocol number: 56733164-203-E.5863).
Clinical trial registration statement: Our study is a pilot study, not a randomized controlled study. Therefore, the study was not registered. We aim for this study to be a pioneer for the randomized studies we will conduct in the future. We will register the randomized controlled studies we will conduct through the system prior the enrollment.
Informed consent statement: There is human subject 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.
Data sharing statement: No additional data are available.
CONSORT 2010 statement: The authors have read the CONSORT 2010 Statement, and the manuscript was prepared and revised according to the CONSORT 2010 Statement.
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: Erdinç Civelek, MD, Full Professor, Department of Neurosurgery, University of Health Sciences, Gaziosmanpaşa Training and Research Hospital, Karayolları Mahallesi, Osmanbey Caddesi 616. Sokak No. 10, Gaziosmanpaşa 34255, Istanbul, Turkey. civsurgeon@yahoo.com
Received: October 23, 2023
Peer-review started: October 23, 2023
First decision: November 13, 2023
Revised: November 30, 2023
Accepted: January 5, 2024
Article in press: January 5, 2024
Published online: January 26, 2024
Abstract
BACKGROUND

Peripheral nerve injury can result in significant clinical complications that have uncertain prognoses. Currently, there is a lack of effective pharmacological interventions for nerve damage, despite the existence of several small compounds, peptides, hormones, and growth factors that have been suggested as potential enhancers of neuron regeneration. Despite the objective of achieving full functional restoration by surgical intervention, the persistent challenge of inadequate functional recovery remains a significant concern in the context of peripheral nerve injuries.

AIM

To examine the impact of exosomes on the process of functional recovery following a complete radial nerve damage.

METHODS

A male individual, aged 24, who is right-hand dominant and an immigrant, arrived with an injury caused by a knife assault. The cut is located on the left arm, specifically below the elbow. The neurological examination and electrodiagnostic testing reveal evidence of left radial nerve damage. The sural autograft was utilized for repair, followed by the application of 1 mL of mesenchymal stem cell-derived exosome, comprising 5 billion microvesicles. This exosome was split into four equal volumes of 0.25 mL each and delivered microsurgically to both the proximal and distal stumps using the subepineural pathway. The patient was subjected to a period of 180 d during which they had neurological examination and electrodiagnostic testing.

RESULTS

The duration of the patient’s follow-up period was 180 d. An increasing Tinel’s sign and sensory-motor recovery were detected even at the 10th wk following nerve grafting. Upon the conclusion of the 6-mo post-treatment period, an evaluation was conducted to measure the extent of improvement in motor and sensory functions of the nerve. This assessment was based on the British Medical Research Council scale and the Mackinnon-Dellon scale. The results indicated that the level of improvement in motor function was classified as M5, denoting an excellent outcome. Additionally, the level of improvement in sensory function was classified as S3+, indicating a good outcome. It is noteworthy that these assessments were conducted in the absence of physical therapy. At the 10th wk post-injury, despite the persistence of substantial axonal damage, the nerve exhibited indications of nerve re-innervation as evidenced by control electromyography (EMG). In contrast to the preceding. EMG analysis revealed a significant electrophysiological enhancement in the EMG conducted at the 6th-mo follow-up, indicating ongoing regeneration.

CONCLUSION

Enhanced comprehension of the neurobiological ramifications associated with peripheral nerve damage, as well as the experimental and therapy approaches delineated in this investigation, holds the potential to catalyze future clinical progress.

Keywords: Mesenchymal stem cell, Exosomes, Radial nerve, Sural nerve

Core Tip: Peripheral nerve damage can manifest in several contexts, including civil, military, or iatrogenic circumstances. Despite the advancements in microsurgical techniques in recent times, the treatment outcomes for peripheral nerve damage have not yet reached a desirable level. This study investigates the functional recovery of a patient who received a sural nerve transplant and exosome application to treat a whole radial nerve lesion caused by a knife assault. Stem cell-derived treatments, such as the use of exosomes, have the potential to provide a novel and promising outlook for the treatment of peripheral nerve injury.