Systematic Reviews
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Transplant. Mar 18, 2024; 14(1): 89674
Published online Mar 18, 2024. doi: 10.5500/wjt.v14.i1.89674
Current status and future perspectives on stem cell transplantation for spinal cord injury
Edoardo Agosti, Marco Zeppieri, Andrea Pagnoni, Marco Maria Fontanella, Alessandro Fiorindi, Tamara Ius, Pier Paolo Panciani
Edoardo Agosti, Andrea Pagnoni, Alessandro Fiorindi, Pier Paolo Panciani, Division of Neurosurgery, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia 25123, Italy
Marco Zeppieri, Department of Ophthalmology, University Hospital of Udine, Udine 33100, Italy
Marco Maria Fontanella, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia 25123, BS, Italy
Tamara Ius, Neurosurgery Unit, Head-Neck and NeuroScience Department, University Hospital of Udine, Udine 33100, Italy
Author contributions: Agosti E wrote the outline, did the research, wrote the paper, and provided the final approval of the version of the article; Zeppieri M assisted in the conception and design of the study, writing, outline, final approval of the version of the article to be published and completed the English and scientific editing; Maria M Fontanella assisted in the editing and making critical revisions of the manuscript; Alessandro F assisted in the writing, editing and making critical revisions of the manuscript; Tamara Ius assisted in the writing, editing and making critical revisions of the manuscript; Panciani PP assisted in the writing, editing and making critical revisions of the manuscript.
Conflict-of-interest statement: All the author declare no conflict of interests for this article.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
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: Marco Zeppieri, BSc, MD, PhD, Doctor, Department of Ophthalmology, University Hospital of Udine, p.le S. Maria della Misericordia 15, Udine 33100, Italy. markzeppieri@hotmail.com
Received: November 8, 2023
Peer-review started: November 8, 2023
First decision: November 29, 2023
Revised: December 4, 2023
Accepted: December 29, 2023
Article in press: December 29, 2023
Published online: March 18, 2024
Processing time: 127 Days and 14.6 Hours
Abstract
BACKGROUND

Previous assessments of stem cell therapy for spinal cord injuries (SCI) have encountered challenges and constraints. Current research primarily emphasizes safety in early-phase clinical trials, while systematic reviews prioritize effectiveness, often overlooking safety and translational feasibility. This situation prompts inquiries regarding the readiness for clinical adoption.

AIM

To offer an up-to-date systematic literature review of clinical trial results concerning stem cell therapy for SCI.

METHODS

A systematic search was conducted across major medical databases [PubMed, Embase, Reference Citation Analysis (RCA), and Cochrane Library] up to October 14, 2023. The search strategy utilized relevant Medical Subject Heading (MeSH) terms and keywords related to "spinal cord", "injury", "clinical trials", "stem cells", "functional outcomes", and "adverse events". Studies included in this review consisted of randomized controlled trials and non-randomized controlled trials reporting on the use of stem cell therapies for the treatment of SCI.

RESULTS

In a comprehensive review of 66 studies on stem cell therapies for SCI, 496 papers were initially identified, with 237 chosen for full-text analysis. Among them, 236 were deemed eligible after excluding 170 for various reasons. These studies encompassed 1086 patients with varying SCI levels, with cervical injuries being the most common (42.2%). Bone marrow stem cells were the predominant stem cell type used (71.1%), with various administration methods. Follow-up durations averaged around 84.4 months. The 32.7% of patients showed functional improvement from American spinal injury association Impairment Scale (AIS) A to B, 40.8% from AIS A to C, 5.3% from AIS A to D, and 2.1% from AIS B to C. Sensory improvements were observed in 30.9% of patients. A relatively small number of adverse events were recorded, including fever (15.1%), headaches (4.3%), muscle tension (3.1%), and dizziness (2.6%), highlighting the potential for SCI recovery with stem cell therapy.

CONCLUSION

In the realm of SCI treatment, stem cell-based therapies show promise, but clinical trials reveal potential adverse events and limitations, underscoring the need for meticulous optimization of transplantation conditions and parameters, caution against swift clinical implementation, a deeper understanding of SCI pathophysiology, and addressing ethical, tumorigenicity, immunogenicity, and immunotoxicity concerns before gradual and careful adoption in clinical practice.

Keywords: Spinal cord injury; Stem cell therapy; Adverse events; Functional outcomes; Systematic review

Core Tip: In the context of spinal cord injury (SCI) treatment, stem cell-based therapies exhibit promise, as demonstrated in this systematic review of 66 studies. However, the research reveals potential adverse events and limitations, emphasizing the importance of optimizing transplantation conditions, cautious clinical implementation, a deeper understanding of SCI pathophysiology, and addressing ethical, tumorigenicity, immunogenicity, and immunotoxicity concerns before a gradual and careful adoption of stem cell therapy in clinical practice. This underscores the need for further research to ensure the safety and effectiveness of these therapies for SCI patients, while acknowledging their potential for improving functional outcomes.