scholarly journals Practical considerations concerning the use of stem cells for peripheral nerve repair

2009 ◽  
Vol 26 (2) ◽  
pp. E2 ◽  
Author(s):  
Sarah Walsh ◽  
_ _ ◽  
Rajiv Midha
Keyword(s):  
Stem Cells ◽  
Peripheral Nerve ◽  
Schwann Cells ◽  
Nerve Injury ◽  
Cell Fate ◽  
Peripheral Nerves ◽  
Nerve Repair ◽  
Precursor Cells ◽  
Host Cells ◽  
Injured Nerve

In this review the authors intend to demonstrate the need for supplementing conventional repair of the injured nerve with alternative therapies, namely transplantation of stem or progenitor cells. Although peripheral nerves do exhibit the potential to regenerate axons and reinnervate the end organ, outcome following severe nerve injury, even after repair, remains relatively poor. This is likely because of the extensive injury zone that prevents axon outgrowth. Even if outgrowth does occur, a relatively slow growth rate of regeneration results in prolonged denervation of the distal nerve. Whereas denervated Schwann cells (SCs) are key players in the early regenerative success of peripheral nerves, protracted loss of axonal contact renders Schwann cells unreceptive for axonal regeneration. Given that denervated Schwann cells appear to become effete, one logical approach is to support the distal denervated nerve environment by replacing host cells with those derived exogenously. A number of different sources of stem/precursor cells are being explored for their potential application in the scenario of peripheral nerve injury. The most promising candidate, transplant cells are derived from easily accessible sources such as the skin, bone marrow, or adipose tissue, all of which have demonstrated the capacity to differentiate into Schwann cell–like cells. Although recent studies have shown that stem cells can act as promising and beneficial adjuncts to nerve repair, considerable optimization of these therapies will be required for their potential to be realized in a clinical setting. The authors investigate the relevance of the delivery method (both the number and differentiation state of cells) on experimental outcomes, and seek to clarify whether stem cells must survive and differentiate in the injured nerve to convey a therapeutic effect. As our laboratory uses skin-derived precursor cells (SKPCs) in various nerve injury paradigms, we relate our findings on cell fate to other published studies to demonstrate the need to quantify stem cell survival and differentiation for future studies.

scholarly journals The macrophage response to central and peripheral nerve injury. A possible role for macrophages in regeneration.

1987 ◽  
Vol 165 (4) ◽  
pp. 1218-1223 ◽  
Author(s):  
V H Perry ◽  
M C Brown ◽  
S Gordon
Keyword(s):  
Optic Nerve ◽  
Peripheral Nerve ◽  
Schwann Cells ◽  
Nerve Injury ◽  
Peripheral Nerves ◽  
Peripheral Nerve Injury ◽  
Macrophage Response ◽  
Large Numbers ◽  
Myelin Degradation ◽  
Degenerating Axons

Using mAbs and immunocytochemistry we have examined the response of macrophages (M phi) after crush injury to the sciatic or optic nerve in the mouse and rat. We have established that large numbers of M phi enter peripheral nerves containing degenerating axons; the M phi are localized to the portion containing damaged axons, and they phagocytose myelin. The period of recruitment of the M phi in the peripheral nerve is before and during the period of maximal proliferation of the Schwann cells. In contrast, the degenerating optic nerve attracts few M phi, and the removal of myelin is much slower. These results show the clearly different responses of M phi to damage in the central and peripheral nervous systems, and suggest that M phi may be an important component of subsequent repair as well as myelin degradation.

scholarly journals ATP Release through Lysosomal Exocytosis from Peripheral Nerves: The Effect of Lysosomal Exocytosis on Peripheral Nerve Degeneration and Regeneration after Nerve Injury

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Junyang Jung ◽  
Hyun Woo Jo ◽  
Hyunseob Kwon ◽  
Na Young Jeong
Keyword(s):  
Peripheral Nerve ◽  
Schwann Cells ◽  
Nerve Injury ◽  
Peripheral Nerves ◽  
Wallerian Degeneration ◽  
Atp Release ◽  
Nerve Degeneration ◽  
Peripheral Neurons ◽  
Charcot Marie Tooth Disease ◽  
Axonal Degradation

Studies have shown that lysosomal activation increases in Schwann cells after nerve injury. Lysosomal activation is thought to promote the engulfment of myelin debris or fragments of injured axons in Schwann cells during Wallerian degeneration. However, a recent interpretation of lysosomal activation proposes a different view of the phenomenon. During Wallerian degeneration, lysosomes become secretory vesicles and are activated for lysosomal exocytosis. The lysosomal exocytosis triggers adenosine 5′-triphosphate (ATP) release from peripheral neurons and Schwann cells during Wallerian degeneration. Exocytosis is involved in demyelination and axonal degradation, which facilitate nerve regeneration following nerve degeneration. At this time, released ATP may affect the communication between cells in peripheral nerves. In this review, our description of the relationship between lysosomal exocytosis and Wallerian degeneration has implications for the understanding of peripheral nerve degenerative diseases and peripheral neuropathies, such as Charcot-Marie-Tooth disease or Guillain-Barré syndrome.

AN ECLECTIC REVIEW OF THE HISTORY OF PERIPHERAL NERVE SURGERY

Neurosurgery ◽  
2009 ◽  
Vol 65 (suppl_4) ◽  
pp. A3-A8 ◽  
Author(s):  
Allan H. Friedman
Keyword(s):  
Peripheral Nerve ◽  
Peripheral Nerves ◽  
Nerve Repair ◽  
Lessons Learned ◽  
Injured Nerve ◽  
Peripheral Nerve Surgery ◽  
Distinguished Career ◽  
History Of ◽  
Nerve Surgery

Abstract WE TAKE OUR present concepts of nerve repair for granted. In fact, the pioneers who established these principles traveled a road filled with erroneous dogma, bad advice, and misleading data. The lessons learned from a review of the history of peripheral nerve surgery are applicable to all neurosurgical disciplines. In honor of Dr. David Kline's distinguished career, we will review 3 aspects of the history of peripheral nerve surgery: Can an injured nerve regain function? How do peripheral nerves regenerate? When should a neuroma in continuity be resected?

scholarly journals Mesenchymal Stem Cell Treatment Perspectives in Peripheral Nerve Regeneration: Systematic Review

2021 ◽  
Vol 22 (2) ◽  
pp. 572
Author(s):  
Andrea Lavorato ◽  
Stefania Raimondo ◽  
Marina Boido ◽  
Luisa Muratori ◽  
Giorgia Durante ◽  
...  
Keyword(s):  
Systematic Review ◽  
Stem Cells ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Nerve Injury ◽  
Nerve Repair ◽  
Peripheral Nerve Regeneration ◽  
High Survival ◽  
Nerve Lesion ◽  
Differentiation Potential

Traumatic peripheral nerve lesions affect hundreds of thousands of patients every year; their consequences are life-altering and often devastating and cause alterations in movement and sensitivity. Spontaneous peripheral nerve recovery is often inadequate. In this context, nowadays, cell therapy represents one of the most innovative approaches in the field of nerve repair therapies. The purpose of this systematic review is to discuss the features of different types of mesenchymal stem cells (MSCs) relevant for peripheral nerve regeneration after nerve injury. The published literature was reviewed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A combination of the keywords “nerve regeneration”, “stem cells”, “peripheral nerve injury”, “rat”, and “human” were used. Additionally, a “MeSH” research was performed in PubMed using the terms “stem cells” and “nerve regeneration”. The characteristics of the most widely used MSCs, their paracrine potential, targeted stimulation, and differentiation potentials into Schwann-like and neuronal-like cells are described in this paper. Considering their ability to support and stimulate axonal growth, their remarkable paracrine activity, their presumed differentiation potential, their extremely low immunogenicity, and their high survival rate after transplantation, ADSCs appear to be the most suitable and promising MSCs for the recovery of peripheral nerve lesion. Clinical considerations are finally reported.

scholarly journals MicroRNA Mediated Regulation of Schwann Cell Migration and Proliferation in Peripheral Nerve Injury

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Eun Jung Sohn ◽  
Hwan Tae Park
Keyword(s):  
Peripheral Nerve ◽  
Nerve Injury ◽  
Peripheral Nerves ◽  
Peripheral Nerve Injury ◽  
Nerve Repair ◽  
Noncoding Rnas ◽  
Potential Therapeutic Target ◽  
Neuronal Disease ◽  
Cell Migration And Proliferation ◽  
Nerve System

Schwann cells (SCs) contribute to nerve repair following injury; however, the underlying molecular mechanism is poorly understood. MicroRNAs (miRNAs), which are short noncoding RNAs, have been shown to play a role in neuronal disease. In this work, we show that miRNAs regulate the peripheral nerve system by modulating the migration and proliferation of SCs. Thus, miRNAs expressed in peripheral nerves may provide a potential therapeutic target for peripheral nerve injury or repair.

scholarly journals Leukemia inhibitory factor regulates Schwann cell proliferation and migration and affects peripheral nerve regeneration

2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Qianqian Chen ◽  
Qianyan Liu ◽  
Yunsong Zhang ◽  
Shiying Li ◽  
Sheng Yi
Keyword(s):  
Schwann Cell ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Schwann Cells ◽  
Nerve Injury ◽  
Peripheral Nerves ◽  
Leukemia Inhibitory Factor ◽  
Peripheral Nerve Regeneration ◽  
And Migration ◽  
Proliferation And Migration

AbstractLeukemia inhibitory factor (LIF) is a pleiotropic cytokine that stimulates neuronal development and survival. Our previous study has demonstrated that LIF mRNA is dysregulated in the peripheral nerve segments after nerve injury. Here, we show that LIF protein is abundantly expressed in Schwann cells after rat sciatic nerve injury. Functionally, suppressed or elevated LIF increases or decreases the proliferation rate and migration ability of Schwann cells, respectively. Morphological observations demonstrate that in vivo application of siRNA against LIF after peripheral nerve injury promotes Schwann cell migration and proliferation, axon elongation, and myelin formation. Electrophysiological and behavior assessments disclose that knockdown of LIF benefits the function recovery of injured peripheral nerves. Differentially expressed LIF affects the metabolism of Schwann cells and negatively regulates ERFE (Erythroferrone). Collectively, our observations reveal the essential roles for LIF in regulating the proliferation and migration of Schwann cells and the regeneration of injured peripheral nerves, discover ERFE as a downstream effector of LIF, and extend our understanding of the molecular mechanisms underlying peripheral nerve regeneration.

scholarly journals Past, Present, and Future of Nerve Conduits in the Treatment of Peripheral Nerve Injury

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Aikeremujiang Muheremu ◽  
Qiang Ao
Keyword(s):  
Stem Cells ◽  
Clinical Practice ◽  
Peripheral Nerve ◽  
Schwann Cells ◽  
Nerve Injury ◽  
Neurotrophic Factors ◽  
Peripheral Nerve Injury ◽  
Functional Outcomes ◽  
Nerve Conduits ◽  
New Construction

With significant advances in the research and application of nerve conduits, they have been used to repair peripheral nerve injury for several decades. Nerve conduits range from biological tubes to synthetic tubes, and from nondegradable tubes to biodegradable tubes. Researchers have explored hollow tubes, tubes filled with scaffolds containing neurotrophic factors, and those seeded with Schwann cells or stem cells. The therapeutic effect of nerve conduits is improving with increasing choice of conduit material, new construction of conduits, and the inclusion of neurotrophic factors and support cells in the conduits. Improvements in functional outcomes are expected when these are optimized for use in clinical practice.

scholarly journals Obestatin signaling controls Schwann cells and axonal transport to counteract neuromuscular synaptic loss in skeletal muscle

2020 ◽  
Author(s):  
Jesus P Camiña ◽  
Agustín Sánchez-Temprano ◽  
Saúl Leal-López ◽  
Jessica González-Sánchez ◽  
Carlos S. Mosteiro ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Peripheral Nerve ◽  
Schwann Cells ◽  
Nerve Injury ◽  
Nerve Repair ◽  
Axon Growth ◽  
Neuromuscular Synapses ◽  
Axonal Regrowth ◽  
Peripheral Nerve System ◽  
Nerve System

Abstract Background. Injuries to the peripheral nerve system are common conditions, with broad spectrum of symptoms depending on the impaired nerves and severity of damage. Although peripheral nervous system retains a remarkable ability for regeneration, it is estimated that less than ten percent of patients fully recover function after nerve injury and the available treatments remain suboptimal. Here, we identify a role for the obestatin/GPR39 system in the regulation of the Schwann cell plasticity as well as in the preservation of neuromuscular synapses in the course of nerve repair. Methods. Utilizing a compression model of sciatic nerve injury, axonotmesis, we assessed the obestatin-related regenerative response in the peripheral nerve system. The role of the obestatin/GPR39 system was further evaluated on immortalized rat Schwann cells, IFRS1, and the model of neuronal differentiation, PC12 cells. The interactions between SCs and neurons was evaluated using a co-culture system that combine the SC cell line IFRS1 and the NGF-primed PC12. Results. Obestatin signaling directs proliferation and migration of Schwann cells that sustain axonal regrowth and later remyelinate regenerated axons. We provide evidence supporting the preservation of skeletal muscle by the maintenance of neuromuscular synapses through the axonal regulation of calpain-calpastatin proteolytic system. This encompasses the control of skeletal muscle homeostasis by regulation of the ubiquitin proteasome system and the autophagy machinery. Conclusions. These results provide important insights into how the obestatin/GPR39 system promotes nerve repair through integration of multiple molecular cues of neuron-Schwann cells crosstalk aimed to promote axon growth and guide axons back to their targets.

scholarly journals Characteristics of cytokines in regeneration of injured peripheral nerves

2020 ◽  
Author(s):  
Ruirui Zhang ◽  
Sailing Chen ◽  
Yinying Shen ◽  
Sheng Yi ◽  
Hui Xu
Keyword(s):  
Immune Responses ◽  
Peripheral Nerve ◽  
Nerve Injury ◽  
Peripheral Nerves ◽  
Nerve Repair ◽  
Expression Patterns ◽  
Differentially Expressed ◽  
Sequencing Data ◽  
Peripheral Nerve Repair ◽  
Time Points

Abstract Background Cytokines are essential cellular modulators of a variety of physiological and pathological activities, including peripheral nerve repair and regeneration. However, the molecular changes of these cellular mediators during peripheral nerve regeneration are not well clarified. The study is aimed to discover critical cytokines for the regenerative process of injured peripheral nerves. Methods The sequencing data of the injured nerve stumps and the dorsal root ganglia (DRGs) of Sprague-Dawley (SD) rats subjected to sciatic nerve (SN) crush injury was analyzed to determine expression patterns of genes coding for cytokines. PCR experiments were used to validate the accuracy of sequencing data. Results A total of 46, 52, and 54 upstream cytokines were differentially expressed in SNs at 1 day, 4 days, and 7 days after nerve injury. And a total of 25, 28, and 34 upstream cytokines were differentially expressed in DRGs at these time points. The expression patterns of some essential upstream cytokines were displayed in a heatmap and validated by PCR experiment. Bioinformatic analysis of these differentially expressed upstream cytokines after nerve injury demonstrated that inflammatory and immune responses were significantly involved. Conclusions In summary, the findings provided an overview of the dynamic changes of cytokines in SNs and DRGs at different time points after rat nerve crush injury, elucidated the biological processes of differentially expressed cytokines, especially the important roles in inflammatory and immune responses during peripheral nerve repair and regeneration, and thus might contribute to identification of potential treatments for peripheral nerve repair and regeneration.

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