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Special Issue "Peripheral Nerve Regeneration: From Bench to Bedside"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 December 2016)

Special Issue Editor

Guest Editor
Assoc. Prof. Dr. Xiaofeng Jia

Department of Neurosurgery, Orthopaedics, University of Maryland School of Medicine, Department of Biomedical Engineering, Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, 10 South Pine Street, MSTF RM 5-59, Baltimore, MD 21201, USA
Website | E-Mail
Interests: brain monitoring and therapeutic hypothermia; peripheral nerve injury and regeneration; translational therapeutic model for neurological injuries; development and characterization of biomaterials for bone and peripheral nerve regeneration

Special Issue Information

Dear Colleagues,

Peripheral nerve injuries remain a significant source of long lasting morbidity, disability, and economics costs. Much research continues to be performed in areas related to improving the surgical outcomes of peripheral nerve repair. Although many approaches to enhance peripheral nerve regeneration have not outperformed the ‘gold standard' set by autograft procedures, studies over the past few decades have resulted in several clinically available bioabsorbable conduits and novel peripheral nerve interfaces. Among the most exciting research areas, stem cell biology recently burst out and holds significant promise in the repair of neurological injuries. The understanding of stem cell differentiation, homing, neurotrophic factors secretion and novel repair material, and the ability to mobilize endogenous stem cells to assist peripheral nerve regeneration constitute key points of research interest in nerve regeneration.

The goal of this special issue is to provide a summary of the field, describe its impact as well as introduce the recent advances in the basic and translational research of peripheral nerve injury from bench to bedside. We invite authors to submit original research and review articles related to peripheral nerve injury; mainly basic and translational research, but also clinical studies. We are interested in articles that explore the advances in neuroengineering and latest technologies in promoting peripheral nerve regeneration from translational model to clinical evaluation, such as electrophysiological monitoring and optogenesis technique. This issue will address novel therapeutic intervention in humans and also in animal models, and seek to determine the role of stem cells from widespread sources in the complex process of peripheral nerve regeneration.

Prof. Dr. Xiaofeng Jia
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • peripheral nerve injury
  • nerve regeneration
  • stem cell
  • nerve scaffold
  • 3D printing
  • growth factors
  • electrophysiology
  • cell biology
  • signaling pathway
  • optogenesis
  • translational model
  • functional outcome
  • neuroengineering
  • clinical evaluation

Related Special Issue

Published Papers (6 papers)

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Research

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Open AccessArticle Transplantation of Embryonic Spinal Cord Derived Cells Helps to Prevent Muscle Atrophy after Peripheral Nerve Injury
Int. J. Mol. Sci. 2017, 18(3), 511; doi:10.3390/ijms18030511
Received: 26 December 2016 / Revised: 10 February 2017 / Accepted: 22 February 2017 / Published: 27 February 2017
PDF Full-text (6315 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Injuries to peripheral nerves are frequent in serious traumas and spinal cord injuries. In addition to surgical approaches, other interventions, such as cell transplantation, should be considered to keep the muscles in good condition until the axons regenerate. In this study, E14.5 rat
[...] Read more.
Injuries to peripheral nerves are frequent in serious traumas and spinal cord injuries. In addition to surgical approaches, other interventions, such as cell transplantation, should be considered to keep the muscles in good condition until the axons regenerate. In this study, E14.5 rat embryonic spinal cord fetal cells and cultured neural progenitor cells from different spinal cord segments were injected into transected musculocutaneous nerve of 200–300 g female Sprague Dawley (SD) rats, and atrophy in biceps brachii was assessed. Both kinds of cells were able to survive, extend their axons towards the muscle and form neuromuscular junctions that were functional in electromyographic studies. As a result, muscle endplates were preserved and atrophy was reduced. Furthermore, we observed that the fetal cells had a better effect in reducing the muscle atrophy compared to the pure neural progenitor cells, whereas lumbar cells were more beneficial compared to thoracic and cervical cells. In addition, fetal lumbar cells were used to supplement six weeks delayed surgical repair after the nerve transection. Cell transplantation helped to preserve the muscle endplates, which in turn lead to earlier functional recovery seen in behavioral test and electromyography. In conclusion, we were able to show that embryonic spinal cord derived cells, especially the lumbar fetal cells, are beneficial in the treatment of peripheral nerve injuries due to their ability to prevent the muscle atrophy. Full article
(This article belongs to the Special Issue Peripheral Nerve Regeneration: From Bench to Bedside)
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Open AccessArticle Tonsil-Derived Mesenchymal Stem Cells Differentiate into a Schwann Cell Phenotype and Promote Peripheral Nerve Regeneration
Int. J. Mol. Sci. 2016, 17(11), 1867; doi:10.3390/ijms17111867
Received: 23 August 2016 / Revised: 2 November 2016 / Accepted: 4 November 2016 / Published: 9 November 2016
Cited by 2 | PDF Full-text (6907 KB) | HTML Full-text | XML Full-text
Abstract
Schwann cells (SCs), which produce neurotropic factors and adhesive molecules, have been reported previously to contribute to structural support and guidance during axonal regeneration; therefore, they are potentially a crucial target in the restoration of injured nervous tissues. Autologous SC transplantation has been
[...] Read more.
Schwann cells (SCs), which produce neurotropic factors and adhesive molecules, have been reported previously to contribute to structural support and guidance during axonal regeneration; therefore, they are potentially a crucial target in the restoration of injured nervous tissues. Autologous SC transplantation has been performed and has shown promising clinical results for treating nerve injuries and donor site morbidity, and insufficient production of the cells have been considered as a major issue. Here, we performed differentiation of tonsil-derived mesenchymal stem cells (T-MSCs) into SC-like cells (T-MSC-SCs), to evaluate T-MSC-SCs as an alternative to SCs. Using SC markers such as CAD19, GFAP, MBP, NGFR, S100B, and KROX20 during quantitative real-time PCR we detected the upregulation of NGFR, S100B, and KROX20 and the downregulation of CAD19 and MBP at the fully differentiated stage. Furthermore, we found myelination of axons when differentiated SCs were cocultured with mouse dorsal root ganglion neurons. The application of T-MSC-SCs to a mouse model of sciatic nerve injury produced marked improvements in gait and promoted regeneration of damaged nerves. Thus, the transplantation of human T-MSCs might be suitable for assisting in peripheral nerve regeneration. Full article
(This article belongs to the Special Issue Peripheral Nerve Regeneration: From Bench to Bedside)
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Review

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Open AccessReview Role of Netrin-1 Signaling in Nerve Regeneration
Int. J. Mol. Sci. 2017, 18(3), 491; doi:10.3390/ijms18030491
Received: 14 December 2016 / Revised: 20 February 2017 / Accepted: 22 February 2017 / Published: 24 February 2017
Cited by 3 | PDF Full-text (4655 KB) | HTML Full-text | XML Full-text
Abstract
Netrin-1 was the first axon guidance molecule to be discovered in vertebrates and has a strong chemotropic function for axonal guidance, cell migration, morphogenesis and angiogenesis. It is a secreted axon guidance cue that can trigger attraction by binding to its canonical receptors
[...] Read more.
Netrin-1 was the first axon guidance molecule to be discovered in vertebrates and has a strong chemotropic function for axonal guidance, cell migration, morphogenesis and angiogenesis. It is a secreted axon guidance cue that can trigger attraction by binding to its canonical receptors Deleted in Colorectal Cancer (DCC) and Neogenin or repulsion through binding the DCC/Uncoordinated (Unc5) A–D receptor complex. The crystal structures of Netrin-1/receptor complexes have recently been revealed. These studies have provided a structure based explanation of Netrin-1 bi-functionality. Netrin-1 and its receptor are continuously expressed in the adult nervous system and are differentially regulated after nerve injury. In the adult spinal cord and optic nerve, Netrin-1 has been considered as an inhibitor that contributes to axon regeneration failure after injury. In the peripheral nervous system, Netrin-1 receptors are expressed in Schwann cells, the cell bodies of sensory neurons and the axons of both motor and sensory neurons. Netrin-1 is expressed in Schwann cells and its expression is up-regulated after peripheral nerve transection injury. Recent studies indicated that Netrin-1 plays a positive role in promoting peripheral nerve regeneration, Schwann cell proliferation and migration. Targeting of the Netrin-1 signaling pathway could develop novel therapeutic strategies to promote peripheral nerve regeneration and functional recovery. Full article
(This article belongs to the Special Issue Peripheral Nerve Regeneration: From Bench to Bedside)
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Open AccessReview The Glia Response after Peripheral Nerve Injury: A Comparison between Schwann Cells and Olfactory Ensheathing Cells and Their Uses for Neural Regenerative Therapies
Int. J. Mol. Sci. 2017, 18(2), 287; doi:10.3390/ijms18020287
Received: 4 December 2016 / Revised: 14 January 2017 / Accepted: 17 January 2017 / Published: 29 January 2017
Cited by 1 | PDF Full-text (2809 KB) | HTML Full-text | XML Full-text
Abstract
The peripheral nervous system (PNS) exhibits a much larger capacity for regeneration than the central nervous system (CNS). One reason for this difference is the difference in glial cell types between the two systems. PNS glia respond rapidly to nerve injury by clearing
[...] Read more.
The peripheral nervous system (PNS) exhibits a much larger capacity for regeneration than the central nervous system (CNS). One reason for this difference is the difference in glial cell types between the two systems. PNS glia respond rapidly to nerve injury by clearing debris from the injury site, supplying essential growth factors and providing structural support; all of which enhances neuronal regeneration. Thus, transplantation of glial cells from the PNS is a very promising therapy for injuries to both the PNS and the CNS. There are two key types of PNS glia: olfactory ensheathing cells (OECs), which populate the olfactory nerve, and Schwann cells (SCs), which are present in the rest of the PNS. These two glial types share many similar morphological and functional characteristics but also exhibit key differences. The olfactory nerve is constantly turning over throughout life, which means OECs are continuously stimulating neural regeneration, whilst SCs only promote regeneration after direct injury to the PNS. This review presents a comparison between these two PNS systems in respect to normal physiology, developmental anatomy, glial functions and their responses to injury. A thorough understanding of the mechanisms and differences between the two systems is crucial for the development of future therapies using transplantation of peripheral glia to treat neural injuries and/or disease. Full article
(This article belongs to the Special Issue Peripheral Nerve Regeneration: From Bench to Bedside)
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Open AccessReview Stem Cell Transplantation for Peripheral Nerve Regeneration: Current Options and Opportunities
Int. J. Mol. Sci. 2017, 18(1), 94; doi:10.3390/ijms18010094
Received: 15 December 2016 / Revised: 26 December 2016 / Accepted: 27 December 2016 / Published: 5 January 2017
Cited by 4 | PDF Full-text (426 KB) | HTML Full-text | XML Full-text
Abstract
Peripheral nerve regeneration is a complicated process highlighted by Wallerian degeneration, axonal sprouting, and remyelination. Schwann cells play an integral role in multiple facets of nerve regeneration but obtaining Schwann cells for cell-based therapy is limited by the invasive nature of harvesting and
[...] Read more.
Peripheral nerve regeneration is a complicated process highlighted by Wallerian degeneration, axonal sprouting, and remyelination. Schwann cells play an integral role in multiple facets of nerve regeneration but obtaining Schwann cells for cell-based therapy is limited by the invasive nature of harvesting and donor site morbidity. Stem cell transplantation for peripheral nerve regeneration offers an alternative cell-based therapy with several regenerative benefits. Stem cells have the potential to differentiate into Schwann-like cells that recruit macrophages for removal of cellular debris. They also can secrete neurotrophic factors to promote axonal growth, and remyelination. Currently, various types of stem cell sources are being investigated for their application to peripheral nerve regeneration. This review highlights studies involving the stem cell types, the mechanisms of their action, methods of delivery to the injury site, and relevant pre-clinical or clinical data. The purpose of this article is to review the current point of view on the application of stem cell based strategy for peripheral nerve regeneration. Full article
(This article belongs to the Special Issue Peripheral Nerve Regeneration: From Bench to Bedside)
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Open AccessReview Advances and Future Applications of Augmented Peripheral Nerve Regeneration
Int. J. Mol. Sci. 2016, 17(9), 1494; doi:10.3390/ijms17091494
Received: 15 July 2016 / Revised: 30 August 2016 / Accepted: 30 August 2016 / Published: 7 September 2016
Cited by 7 | PDF Full-text (249 KB) | HTML Full-text | XML Full-text
Abstract
Peripheral nerve injuries remain a significant source of long lasting morbidity, disability, and economic costs. Much research continues to be performed in areas related to improving the surgical outcomes of peripheral nerve repair. In this review, the physiology of peripheral nerve regeneration and
[...] Read more.
Peripheral nerve injuries remain a significant source of long lasting morbidity, disability, and economic costs. Much research continues to be performed in areas related to improving the surgical outcomes of peripheral nerve repair. In this review, the physiology of peripheral nerve regeneration and the multitude of efforts to improve surgical outcomes are discussed. Improvements in tissue engineering that have allowed for the use of synthetic conduits seeded with neurotrophic factors are highlighted. Selected pre-clinical and available clinical data using cell based methods such as Schwann cell, undifferentiated, and differentiated stem cell transplantation to guide and enhance peripheral nerve regeneration are presented. The limitations that still exist in the utility of neurotrophic factors and cell-based therapies are outlined. Strategies that are most promising for translation into the clinical arena are suggested. Full article
(This article belongs to the Special Issue Peripheral Nerve Regeneration: From Bench to Bedside)
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