Elsevier

Current Opinion in Neurobiology

Volume 47, December 2017, Pages 52-57
Current Opinion in Neurobiology

Schwann cells as drivers of tissue repair and regeneration

https://doi.org/10.1016/j.conb.2017.09.003Get rights and content

Highlights

  • Dedifferentiated Schwann cells are required for the regeneration of multiple tissues in mammals and amphibians.

  • Dedifferentiated Schwann cells originate from injured nerves and migrate into damaged tissues.

  • Dedifferentiated Schwann cells promote regeneration through paracrine growth factor secretion.

  • Sox2 expression regulates dedifferentiated Schwann cell activity during tissue repair and regeneration.

Current evidence suggests that peripheral nerve-associated Schwann cells possess the capacity to promote the repair and regeneration of multiple tissue types, in addition to peripheral nervous system axons. These findings shed light on the nerve-dependent nature of regeneration that has been well documented in various organs. This review outlines recent advances in knowledge surrounding endogenous regenerative functions of Schwann cells across species and tissue types, with a specific focus on the role of Sox2+ dedifferentiated Schwann cells in regulating the proliferation of surrounding tissue-resident mesenchymal precursors.

Introduction

While considerable progress has been made in the field of regenerative medicine over the last decade [1, 2], much still remains to be discovered regarding endogenous mechanisms of tissue repair. Despite our best efforts to capture the healing properties of somatic stem cells, the upstream cues and cell-to-cell interactions that ultimately instruct their activity are generally poorly defined. However, there is accumulating evidence that endogenous tissue-derived precursors are under nervous system control, with Schwann cells coming to the forefront as a ‘pro-regenerative’ cell type. In addition to their well-appreciated functions during peripheral nerve repair, which include remodelling of the damaged axonal environment and promoting guidance of regenerating axons, Schwann cells also possess impressive phenotypic plasticity [3] and likely play an understated role in the regeneration of additional tissues. Consequently, Schwann cells have a continually expanding list of non-canonical functions and represent a novel target of potential therapeutic application.

Section snippets

Schwann cells set the stage for limb regeneration in amphibians

The importance of Schwann cells in tissue regeneration is perhaps most evident in the case of appendage regrowth in amphibians. These classical studies revealed that salamanders are capable of performing spectacular feats of regeneration following the amputation of limbs [4]. However, it was not known until recently that these regenerative events are specifically contingent upon the presence of Schwann cells [5••]. Following amputation, reconstitution of the salamander limb begins with the

Trophic support for digit regeneration: role of dedifferentiated Schwann cells

In mammals, including both rodents and humans [8], the digit tip is one of the only known structures capable of completely regenerating multiple tissue types following injury, in a manner that largely recapitulates appendage regeneration in amphibians. In adult mice, amputation of the distal one-third of the terminal phalangeal element, while preserving the proximal nail components, results in nearly complete regeneration of the lost appendage over the course of 4 weeks [9]. This remarkable

Dedifferentiated Schwann cells coordinate skin repair

As a testament to the diversity of tissues in which DSCs function in a regenerative capacity, recent work has identified a role for their activity in skin wound healing (Figure 2). Much like the digit, skin is home to a multitude of stem and progenitor cell types; which within mammalian skin, reside in distinct dermal, epidermal and hypodermal layers. Thus, skin has a robust capacity for repair and regeneration through the directed actions of these progenitors following wounding [26, 27, 28].

Conclusion

Until recently, Schwann cells were historically accepted to act solely as support cells for nerve axons through their provision of both myelination as well as trophic factors to maintain homeostasis and promote axonal repair following injury. However, in an expanding number of contexts there is increasing evidence that peripheral glia possess much greater regenerative influence than once considered. While recent work has shed light on this novel role for DSCs, dissociating their actions from

Conflict of interest statement

Nothing declared.

References and recommended reading

Papers of particular interest, published within the period of review, have been highlighted as:

  • • of special interest

  • •• of outstanding interest

Acknowledgements

This research was supported by Canadian Institutes of Health Research (CIHR) grant MOP-64211.

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    Permanent address: Department of Applied Human Sciences, Faculty of Science, University of Prince Edward Island, Charlottetown, PE C1A 4P3, Canada.

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