Recent Advances in Schwann Cells

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Medicine".

Deadline for manuscript submissions: closed (28 February 2022) | Viewed by 20124

Special Issue Editors


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Guest Editor
1. Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA
2. Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN, USA
Interests: Schwann cells; in vitro culture; signaling pathways; proliferation; myelination; reprogramming; cell therapy; human models of glia-neuron interactions; bioassays and products

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Guest Editor
Department of Plastic and Reconstructive Surgery, Medical University of Vienna, Vienna, Austria
Interests: Schwann cell plasticity; tumor microenvironment; nerve regeneration; pathologies of the peripheral nervous system

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Guest Editor
Department of Biology, Institute of Biological Sciences, Federal University of Juiz de Fora, Juiz de Fora, MG, Brazil
Interests: axon degeneration/regeneration; demyelination; leprosy neuropathy; peripheral neuropathies; Schwann cell-axonal coupling; Wallerian degeneration

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Guest Editor
Biological Optomechanics (Division Guck), Max Planck Institute for the Science of Light & Max-Planck-Zentrum für Physik und Medizin, Staudtstr. 2, 91058 Erlangen, Germany
Interests: neuron and Schwann cell mechanobiology; mechanosensation; cell and tissue biophysics; 3D in vitro culture system

Special Issue Information

Dear Colleagues,

We are pleased to announce the upcoming Special Issue entitled Recent Advances in Schwann Cells. This Special Issue aims to cover a wide range of topics in which biomolecules are used to investigate or target Schwann cells at the molecular, cellular, and organismal levels.

Schwann cells are ubiquitous glial cells spanning the peripheral nervous system. Though Schwann cells are mostly known for their elaborate myelin sheath and role in facilitating electrical conduction, their functions in the body are multiple and not restricted to ensheathment and myelination. These glial cells are among the largest cells in the mammalian body and are endowed with extraordinary plasticity for functional integration to essentially all tissues. Schwann cells are crucial for the metabolic maintenance of long-projecting axons and play an active role during nerve fiber regeneration and remyelination, which provides a basis for using them in regenerative medicine and nervous system repair strategies. Schwann cells are remarkable for their capacity to associate with and thereby modulate the responses of neuronal cells, the immune system, the vasculature, the surrounding extracellular matrix (ECM), and possibly other glial and nonglial cell types depending on context. The versatile functions of Schwann cells rely on the rich and adaptable nature of their biomolecular repertoire that allows them to establish complex interactions with other cells and the physical environment.

In this Special Issue of Biomolecules, we encourage researchers from all disciplines to share research updates contributing to our increased understanding of molecules of all sorts and their role in Schwann cells' function in health and disease. Selected topics appropriate for this issue may include but are not restricted to those listed below:

- Biochemical and biophysical studies on the biosynthesis, maintenance, and remodeling of peripheral (Schwann) myelin- and ECM-associated molecules, molecular pathways targeting Schwann cells survival, proliferation, differentiation, and reprogramming;

- Biosynthesis, secretion and regulation of Schwann cells-specific adhesion molecules, receptors, soluble growth factors, chemoattractants, antigenic factors, exosomes, and other molecules mediating cell–cell or cell–ECM interactions, and other possible Schwann cells responses;

- Genetic and non-genetic manipulation of Schwann cells, development of in vitro and in vivo models, pharmacological and toxicological studies;

- Schwann cells ‘omics’ (metabolomics, proteomics, transcriptomics, lipidomics);

- Schwann cells-specific genes/molecules/pathways affected by disease, druggable Schwann cells-specific targets, platforms, chemical and genetic screens;

- Biomolecules and biomaterials in Schwann cells engineering; molecular tools to study, modify or derive Schwann cells in vitro or in vivo.

Dr. Paula V. Monje
Dr. Tamara Weiss
Dr. Bruno Siqueira Mietto
Dr. Gonzalo Rosso
Guest Editors

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 submissions that pass pre-check are 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. Biomolecules 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 2700 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

  • glia–neuron or glia–nerve interactions
  • myelin
  • extracellular matrix
  • peripheral nerve
  • peripheral neuropathy, cancer, demyelinating disease
  • cell/tissue therapies

Published Papers (6 papers)

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Research

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21 pages, 4098 KiB  
Article
Occurrence of Lymphangiogenesis in Peripheral Nerve Autografts Contrasts Schwann Cell-Induced Apoptosis of Lymphatic Endothelial Cells In Vitro
by Carina Hromada, Jaana Hartmann, Johannes Oesterreicher, Anton Stoiber, Anna Daerr, Barbara Schädl, Eleni Priglinger, Andreas H. Teuschl-Woller, Wolfgang Holnthoner, Johannes Heinzel and David Hercher
Biomolecules 2022, 12(6), 820; https://doi.org/10.3390/biom12060820 - 12 Jun 2022
Cited by 7 | Viewed by 2707
Abstract
Peripheral nerve injuries pose a major clinical concern world-wide, and functional recovery after segmental peripheral nerve injury is often unsatisfactory, even in cases of autografting. Although it is well established that angiogenesis plays a pivotal role during nerve regeneration, the influence of lymphangiogenesis [...] Read more.
Peripheral nerve injuries pose a major clinical concern world-wide, and functional recovery after segmental peripheral nerve injury is often unsatisfactory, even in cases of autografting. Although it is well established that angiogenesis plays a pivotal role during nerve regeneration, the influence of lymphangiogenesis is strongly under-investigated. In this study, we analyzed the presence of lymphatic vasculature in healthy and regenerated murine peripheral nerves, revealing that nerve autografts contained increased numbers of lymphatic vessels after segmental damage. This led us to elucidate the interaction between lymphatic endothelial cells (LECs) and Schwann cells (SCs) in vitro. We show that SC and LEC secretomes did not influence the respective other cell types’ migration and proliferation in 2D scratch assay experiments. Furthermore, we successfully created lymphatic microvascular structures in SC-embedded 3D fibrin hydrogels, in the presence of supporting cells; whereas SCs seemed to exert anti-lymphangiogenic effects when cultured with LECs alone. Here, we describe, for the first time, increased lymphangiogenesis after peripheral nerve injury and repair. Furthermore, our findings indicate a potential lymph-repellent property of SCs, thereby providing a possible explanation for the lack of lymphatic vessels in the healthy endoneurium. Our results highlight the importance of elucidating the molecular mechanisms of SC–LEC interaction. Full article
(This article belongs to the Special Issue Recent Advances in Schwann Cells)
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19 pages, 25849 KiB  
Article
Curcumin and Ethanol Effects in Trembler-J Schwann Cell Culture
by Lucia Vázquez Alberdi, Gonzalo Rosso, Lucía Velóz, Carlos Romeo, Joaquina Farias, María Vittoria Di Tomaso, Miguel Calero and Alejandra Kun
Biomolecules 2022, 12(4), 515; https://doi.org/10.3390/biom12040515 - 29 Mar 2022
Cited by 3 | Viewed by 3032
Abstract
Charcot-Marie-Tooth (CMT) syndrome is the most common progressive human motor and sensory peripheral neuropathy. CMT type 1E is a demyelinating neuropathy affecting Schwann cells due to peripheral-myelin-protein-22 (PMP22) mutations, modelized by Trembler-J mice. Curcumin, a natural polyphenol compound obtained from turmeric (Curcuma [...] Read more.
Charcot-Marie-Tooth (CMT) syndrome is the most common progressive human motor and sensory peripheral neuropathy. CMT type 1E is a demyelinating neuropathy affecting Schwann cells due to peripheral-myelin-protein-22 (PMP22) mutations, modelized by Trembler-J mice. Curcumin, a natural polyphenol compound obtained from turmeric (Curcuma longa), exhibits dose- and time-varying antitumor, antioxidant and neuroprotective properties, however, the neurotherapeutic actions of curcumin remain elusive. Here, we propose curcumin as a possible natural treatment capable of enhancing cellular detoxification mechanisms, resulting in an improvement of the neurodegenerative Trembler-J phenotype. Using a refined method for obtaining enriched Schwann cell cultures, we evaluated the neurotherapeutic action of low dose curcumin treatment on the PMP22 expression, and on the chaperones and autophagy/mammalian target of rapamycin (mTOR) pathways in Trembler-J and wild-type genotypes. In wild-type Schwann cells, the action of curcumin resulted in strong stimulation of the chaperone and macroautophagy pathway, whereas the modulation of ribophagy showed a mild effect. However, despite the promising neuroprotective effects for the treatment of neurological diseases, we demonstrate that the action of curcumin in Trembler-J Schwann cells could be impaired due to the irreversible impact of ethanol used as a common curcumin vehicle necessary for administration. These results contribute to expanding our still limited understanding of PMP22 biology in neurobiology and expose the intrinsic lability of the neurodegenerative Trembler-J genotype. Furthermore, they unravel interesting physiological mechanisms of cellular resilience relevant to the pharmacological treatment of the neurodegenerative Tremble J phenotype with curcumin and ethanol. We conclude that the analysis of the effects of the vehicle itself is an essential and inescapable step to comprehensibly assess the effects and full potential of curcumin treatment for therapeutic purposes. Full article
(This article belongs to the Special Issue Recent Advances in Schwann Cells)
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23 pages, 2204 KiB  
Article
Colocalization Analysis of Peripheral Myelin Protein-22 and Lamin-B1 in the Schwann Cell Nuclei of Wt and TrJ Mice
by María Vittoria Di Tomaso, Lucía Vázquez Alberdi, Daniela Olsson, Saira Cancela, Anabel Fernández, Juan Carlos Rosillo, Ana Laura Reyes Ábalos, Magdalena Álvarez Zabaleta, Miguel Calero and Alejandra Kun
Biomolecules 2022, 12(3), 456; https://doi.org/10.3390/biom12030456 - 16 Mar 2022
Cited by 5 | Viewed by 5060
Abstract
Myelination of the peripheral nervous system requires Schwann cells (SC) differentiation into the myelinating phenotype. The peripheral myelin protein-22 (PMP22) is an integral membrane glycoprotein, expressed in SC. It was initially described as a growth arrest-specific (gas3) gene product, up-regulated by [...] Read more.
Myelination of the peripheral nervous system requires Schwann cells (SC) differentiation into the myelinating phenotype. The peripheral myelin protein-22 (PMP22) is an integral membrane glycoprotein, expressed in SC. It was initially described as a growth arrest-specific (gas3) gene product, up-regulated by serum starvation. PMP22 mutations were pathognomonic for human hereditary peripheral neuropathies, including the Charcot-Marie-Tooth disease (CMT). Trembler-J (TrJ) is a heterozygous mouse model carrying the same pmp22 point mutation as a CMT1E variant. Mutations in lamina genes have been related to a type of peripheral (CMT2B1) or central (autosomal dominant leukodystrophy) neuropathy. We explore the presence of PMP22 and Lamin B1 in Wt and TrJ SC nuclei of sciatic nerves and the colocalization of PMP22 concerning the silent heterochromatin (HC: DAPI-dark counterstaining), the transcriptionally active euchromatin (EC), and the nuclear lamina (H3K4m3 and Lamin B1 immunostaining, respectively). The results revealed that the number of TrJ SC nuclei in sciatic nerves was greater, and the SC volumes were smaller than those of Wt. The myelin protein PMP22 and Lamin B1 were detected in Wt and TrJ SC nuclei and predominantly in peripheral nuclear regions. The level of PMP22 was higher, and those of Lamin B1 lower in TrJ than in Wt mice. The level of PMP22 was higher, and those of Lamin B1 lower in TrJ than in Wt mice. PMP22 colocalized more with Lamin B1 and with the transcriptionally competent EC, than the silent HC with differences between Wt and TrJ genotypes. The results are discussed regarding the probable nuclear role of PMP22 and the relationship with TrJ neuropathy. Full article
(This article belongs to the Special Issue Recent Advances in Schwann Cells)
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14 pages, 3750 KiB  
Article
Notch Signal Mediates the Cross-Interaction between M2 Muscarinic Acetylcholine Receptor and Neuregulin/ErbB Pathway: Effects on Schwann Cell Proliferation
by Roberta Piovesana, Annalinda Pisano, Simona Loreti, Ruggero Ricordy, Claudio Talora and Ada Maria Tata
Biomolecules 2022, 12(2), 239; https://doi.org/10.3390/biom12020239 - 01 Feb 2022
Cited by 2 | Viewed by 1656
Abstract
The cross-talk between axon and glial cells during development and in adulthood is mediated by several molecules. Among them are neurotransmitters and their receptors, which are involved in the control of myelinating and non-myelinating glial cell development and physiology. Our previous studies largely [...] Read more.
The cross-talk between axon and glial cells during development and in adulthood is mediated by several molecules. Among them are neurotransmitters and their receptors, which are involved in the control of myelinating and non-myelinating glial cell development and physiology. Our previous studies largely demonstrate the functional expression of cholinergic muscarinic receptors in Schwann cells. In particular, the M2 muscarinic receptor subtype, the most abundant cholinergic receptor expressed in Schwann cells, inhibits cell proliferation downregulating proteins expressed in the immature phenotype and triggers promyelinating differentiation genes. In this study, we analysed the in vitro modulation of the Neuregulin-1 (NRG1)/erbB pathway, mediated by the M2 receptor activation, through the selective agonist arecaidine propargyl ester (APE). M2 agonist treatment significantly downregulates NRG1 and erbB receptors expression, both at transcriptional and protein level, and causes the internalization and intracellular accumulation of the erbB2 receptor. Additionally, starting from our previous results concerning the negative modulation of Notch-active fragment NICD by M2 receptor activation, in this work, we clearly demonstrate that the M2 receptor subtype inhibits erbB2 receptors by Notch-1/NICD downregulation. Our data, together with our previous results, demonstrate the existence of a cross-interaction between the M2 receptor and NRG1/erbB pathway-Notch1 mediated, and that it is responsible for the modulation of Schwann cell proliferation/differentiation. Full article
(This article belongs to the Special Issue Recent Advances in Schwann Cells)
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Review

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15 pages, 1047 KiB  
Review
Advancing Our Understanding of the Chronically Denervated Schwann Cell: A Potential Therapeutic Target?
by Liam A. McMorrow, Adrian Kosalko, Daniel Robinson, Alberto Saiani and Adam J. Reid
Biomolecules 2022, 12(8), 1128; https://doi.org/10.3390/biom12081128 - 17 Aug 2022
Cited by 5 | Viewed by 2209
Abstract
Outcomes for patients following major peripheral nerve injury are extremely poor. Despite advanced microsurgical techniques, the recovery of function is limited by an inherently slow rate of axonal regeneration. In particular, a time-dependent deterioration in the ability of the distal stump to support [...] Read more.
Outcomes for patients following major peripheral nerve injury are extremely poor. Despite advanced microsurgical techniques, the recovery of function is limited by an inherently slow rate of axonal regeneration. In particular, a time-dependent deterioration in the ability of the distal stump to support axonal growth is a major determinant to the failure of reinnervation. Schwann cells (SC) are crucial in the orchestration of nerve regeneration; their plasticity permits the adoption of a repair phenotype following nerve injury. The repair SC modulates the initial immune response, directs myelin clearance, provides neurotrophic support and remodels the distal nerve. These functions are critical for regeneration; yet the repair phenotype is unstable in the setting of chronic denervation. This phenotypic instability accounts for the deteriorating regenerative support offered by the distal nerve stump. Over the past 10 years, our understanding of the cellular machinery behind this repair phenotype, in particular the role of c-Jun, has increased exponentially, creating opportunities for therapeutic intervention. This review will cover the activation of the repair phenotype in SC, the effects of chronic denervation on SC and current strategies to ‘hack’ these cellular pathways toward supporting more prolonged periods of neural regeneration. Full article
(This article belongs to the Special Issue Recent Advances in Schwann Cells)
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14 pages, 793 KiB  
Review
Four Seasons for Schwann Cell Biology, Revisiting Key Periods: Development, Homeostasis, Repair, and Aging
by Gabriela Sardella-Silva, Bruno Siqueira Mietto and Victor Túlio Ribeiro-Resende
Biomolecules 2021, 11(12), 1887; https://doi.org/10.3390/biom11121887 - 15 Dec 2021
Cited by 12 | Viewed by 3749
Abstract
Like the seasons of the year, all natural things happen in stages, going through adaptations when challenged, and Schwann cells are a great example of that. During maturation, these cells regulate several steps in peripheral nervous system development. The Spring of the cell [...] Read more.
Like the seasons of the year, all natural things happen in stages, going through adaptations when challenged, and Schwann cells are a great example of that. During maturation, these cells regulate several steps in peripheral nervous system development. The Spring of the cell means the rise and bloom through organized stages defined by time-dependent regulation of factors and microenvironmental influences. Once matured, the Summer of the cell begins: a high energy stage focused on maintaining adult homeostasis. The Schwann cell provides many neuron-glia communications resulting in the maintenance of synapses. In the peripheral nervous system, Schwann cells are pivotal after injuries, balancing degeneration and regeneration, similarly to when Autumn comes. Their ability to acquire a repair phenotype brings the potential to reconnect axons to targets and regain function. Finally, Schwann cells age, not only by growing old, but also by imposed environmental cues, like loss of function induced by pathologies. The Winter of the cell presents as reduced activity, especially regarding their role in repair; this reflects on the regenerative potential of older/less healthy individuals. This review gathers essential information about Schwann cells in different stages, summarizing important participation of this intriguing cell in many functions throughout its lifetime. Full article
(This article belongs to the Special Issue Recent Advances in Schwann Cells)
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