Systematic Reviews
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Apr 26, 2020; 12(4): 288-302
Published online Apr 26, 2020. doi: 10.4252/wjsc.v12.i4.288
Human umbilical cord derived mesenchymal stem cells in peripheral nerve regeneration
Christine Bojanic, Kendrick To, Bridget Zhang, Christopher Mak, Wasim S Khan
Christine Bojanic, Department of Plastic and Reconstructive Surgery, Cambridge University Hospitals NHS Trust, Cambridge CB2 0QQ, United Kingdom
Kendrick To, Wasim S Khan, Division of Trauma and Orthopaedic Surgery, Addenbrooke's Hospital, University of Cambridge, Cambridge CB2 0QQ, United Kingdom
Bridget Zhang, Christopher Mak, School of Clinical Medicine, University of Cambridge, Cambridge CB2 0QQ, United Kingdom
Author contributions: To K and Khan WS undertook conception and design of the study; Bojanic C wrote the manuscript under the guidance of To K and Khan WS; Zhang B and Mak C conducted risk of bias analysis; all authors reviewed, edited and approved the final manuscript.
Conflict-of-interest statement: All authors declare that they have no conflict of interest.
PRISMA 2009 Checklist statement: The authors declare that the manuscript satisfies the PRISMA 2009 Checklist and the manuscript has been prepared and revised according to the checklist requirements.
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: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Wasim S Khan, CCST, FRCS (Ed), FRCS (Hon), MBChB, MSc, PhD, Lecturer, Surgeon, Division of Trauma and Orthopaedic Surgery, Addenbrooke's Hospital, University of Cambridge, Hills Road, Cambridge CB2 0QQ, United Kingdom. wasimkhan@doctors.org.uk
Received: December 16, 2019
Peer-review started: December 16, 2019
First decision: February 20, 2020
Revised: March 15, 2020
Accepted: March 23, 2020
Article in press: March 23, 2020
Published online: April 26, 2020
Processing time: 132 Days and 6.6 Hours
ARTICLE HIGHLIGHTS
Research background

Peripheral nerve injury can be a debilitating condition. Traditional treatment options are often ineffective. There is an urgent need for new treatment modalities. Mesenchymal stem cell (MSC) transplantation holds promise as a cell-based regenerative approach in treating nerve lesions. MSCs can be sourced from various tissues, and this may affect their regenerative capacity. Here, we appraise the in vivo evidence for the use of human umbilical cord-derived MSCs (UCMSCs) in peripheral nerve regeneration.

Research motivation

There is contention regarding the optimal cell-source for the harvest of MSCs. Some evidence suggests that MSCs from certain tissue types have superior neurogenic capacity. It is critical that we determine the best cell-source for nerve repair, in order to facilitate an efficient production protocol and maximise clinical benefit.

Research objectives

To investigate whether UCMSCs are effective in nerve regeneration in in vivo models of nerve injury.

Research methods

We performed a systematic literature review according to the PRISMA statement. A search was conducted on three databases (PubMed, EMBASE and Web of Science) by two independent investigators from inception to September 2019 for studies examining the use of UCMSCs in in vivo models of nerve injury. The evidence was appraised using Cochrane’s RoB 2.0 Tool.

Research results

A total of 14 studies were included in the review, with a total of 279 subjects. The studies reported that transplantation of human umbilical cord MSCs were effective in regenerating nerve lesions. There were general improvements in histological and functional outcomes. The studies did not report significant complications.

Research conclusions

Human umbilical cord-derived MSCs were effective in repairing nerve lesions in both animal and human models of nerve injury. Additional studies are required to correlate histological outcomes with functional improvements, as not all studies assessed both. More human studies are necessary to inform the efficacy in humans. High quality randomized controlled trials would be instructive in this case. Long-term follow up in these types of study will help inform the safety of MSC transplantation.

Research perspectives

There is limited evidence examining the use of MSCs derived from other tissues in their capacity to regenerate nerve lesions. Further studies comparing different tissue cell-source directly would be highly informative. In vitro studies of MSC-biomaterial scaffolds may aid the development of more efficient MSC delivery methods. As the nature of nerve injury can vary significantly, the approach to transplantation, such as dose delivery may need to be catered to the individual lesion. Studies comparing the effect of MSCs on different in vivo models could help delineate this.