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World J Stem Cells. Jan 26, 2015; 7(1): 11-26
Published online Jan 26, 2015. doi: 10.4252/wjsc.v7.i1.11
Augmenting peripheral nerve regeneration using stem cells: A review of current opinion
Neil G Fairbairn, Amanda M Meppelink, Joanna Ng-Glazier, Mark A Randolph, Jonathan M Winograd
Neil G Fairbairn, Amanda M Meppelink, Joanna Ng-Glazier, Mark A Randolph, Jonathan M Winograd, Department of Plastic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, United States
Author contributions: Fairbairn NG, Meppelink AM and Ng-Glazier J wrote the manuscript; Randolph MA and Winograd JM reviewed and edited the manuscript.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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/
Correspondence to: Dr. Neil G Fairbairn, Department of Plastic Surgery, Massachusetts General Hospital, Harvard Medical School, 15 Parkman Street, Boston, MA 02114, United States. ngf174@hotmail.com
Telephone: +1-617-5152701 Fax: +1-617-7298998
Received: July 27, 2014
Peer-review started: July 27, 2014
First decision: August 14, 2014
Revised: September 15, 2014
Accepted: September 18, 2014
Article in press: December 16, 2014
Published online: January 26, 2015
Processing time: 170 Days and 14.9 Hours
Abstract

Outcomes following peripheral nerve injury remain frustratingly poor. The reasons for this are multifactorial, although maintaining a growth permissive environment in the distal nerve stump following repair is arguably the most important. The optimal environment for axonal regeneration relies on the synthesis and release of many biochemical mediators that are temporally and spatially regulated with a high level of incompletely understood complexity. The Schwann cell (SC) has emerged as a key player in this process. Prolonged periods of distal nerve stump denervation, characteristic of large gaps and proximal injuries, have been associated with a reduction in SC number and ability to support regenerating axons. Cell based therapy offers a potential therapy for the improvement of outcomes following peripheral nerve reconstruction. Stem cells have the potential to increase the number of SCs and prolong their ability to support regeneration. They may also have the ability to rescue and replenish populations of chromatolytic and apoptotic neurons following axotomy. Finally, they can be used in non-physiologic ways to preserve injured tissues such as denervated muscle while neuronal ingrowth has not yet occurred. Aside from stem cell type, careful consideration must be given to differentiation status, how stem cells are supported following transplantation and how they will be delivered to the site of injury. It is the aim of this article to review current opinions on the strategies of stem cell based therapy for the augmentation of peripheral nerve regeneration.

Keywords: Peripheral nerve; Augmentation; Regeneration; Stem cells

Core tip: Outcomes following peripheral nerve injury remain poor. Stem cells may increase Schwann cell numbers and longevity, prolonging their ability to support regeneration. At the level of the cell body, they may have the ability to rescue populations of neurons destined for apoptosis. They may also be used in non-physiologic ways in order to protect muscle targets from the detrimental effects of denervation. Aside from stem cell type, consideration must be given to differentiation status, scaffolding support and the mechanism of delivery. This article reviews current opinion on the strategies of stem cell-based therapy for the augmentation of peripheral nerve regeneration.