Glucose Transporters of Rat Peripheral Nerve: Differential Expression of GLUT1 Gene by Schwann Cells and Perineurial Cells In Vivo and In Vitro

Abstract Salidriside (SDS), a phenylpropanoid glycoside derived from Rhodiola rosea L, has been shown to be neuroprotective in many studies, which may be promising in nerve recovery. In this study, the neuroprotective effects of SDS on engineered nerve constructed by Schwann cells (SCs) and Poly (lactic-co-glycolic acid) (PLGA) were studied in vitro. We further investigated the effect of combinational therapy of SDS and PLGA/SCs based tissue engineering on peripheral nerve regeneration based on the rat model of nerve injury by sciatic transection. The results showed that SDS dramatically enhanced the proliferation and function of SCs. The underlying mechanism may be that SDS affects SCs growth through the modulation of neurotrophic factors (BDNF, GDNF and CNTF). 12 weeks after implantation with a 12 mm gap of sciatic nerve injury, SDS-PLGA/SCs achieved satisfying outcomes of nerve regeneration, as evidenced by morphological and functional improvements upon therapy by SDS, PLGA/SCs or direct suture group assessed by sciatic function index, nerve conduction assay, HE staining and immunohistochemical analysis. Our results demonstrated the significant role of introducing SDS into neural tissue engineering to promote nerve regeneration.

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Upregulated lncARAT in Schwann cells promotes axonal regeneration through recruiting macrophages and inducing macrophages M2 polarization

10.21203/rs.3.rs-543511/v2 ◽

2021 ◽

Author(s):

Gang Yin ◽

Yaofa Lin ◽

Peilin Wang ◽

Jun Zhou ◽

Haodong Lin

Keyword(s):

Peripheral Nerve ◽

Schwann Cells ◽

Axonal Regeneration ◽

Noncoding Rna ◽

Macrophage Polarization ◽

Nerve Repair ◽

M2 Polarization ◽

Sciatic Nerves

Abstract BackgroundAxonal regeneration following peripheral nerve injury largely depends on a favorable microenvironment. Schwann cells (SCs) play a crucial role in axonal regeneration by interacting with macrophages, but the mechanisms underlying macrophages recruitment and polarization remain unclear.MethodsThe total RNA of crushed sciatic nerves and intact contralateral nerves was extracted and used to RNA-sequencing (RNA-seq). The differentially expressed long noncoding RNA (lncRNA) and mRNAs were analyzed using bioinformatics analysis, and were verified using qPCR and western blot analysis. The putative role of lncRNA in nerve regeneration was analyzed in vitro and in vivo. Macrophage polarization phenotype was identified by assessing IL-10, Arg-1, and CD206.ResultsHere we identified an lncRNA, termed Axon Regeneration-Associated Transcript (lncARAT), upregulated in SCs and SCs-derived exosomes after crushed sciatic nerves (CSN). LncARAT contributed to axonal regeneration and improved motor functional recovery. Mechanistically, lncARAT epigenetically activated CCL2 expression by recruiting KMT2A to CCL2 promoter, which resulted in an increased H3K4 trimethylation and CCL2 transcription in SCs. CCL2 upregulation facilitated the infiltration of macrophages into the injured nerves. Meanwhile, lncARAT-enriched exosomes were released from SCs and incorporated into macrophages. Once in macrophage, lncARAT functioned as an endogenous sponge to adsorb miRNA-329-5p, resulting in an increased SOCS2 expression, which facilitated macrophage M2 polarization through a STAT1/6-dependent pathway, thus promoted axonal regeneration.ConclusionsLncARAT may serve as a promising therapeutic avenue for peripheral nerve repair.

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Author Correction: Salidroside promotes peripheral nerve regeneration based on tissue engineering strategy using Schwann cells and PLGA: in vitro and in vivo

Scientific Reports ◽

10.1038/s41598-020-71638-y ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Hui Liu ◽

Peizhen Lv ◽

Yongjia Zhu ◽

Huayu Wu ◽

Kun Zhang ◽

...

Keyword(s):

Tissue Engineering ◽

Peripheral Nerve ◽

Nerve Regeneration ◽

Schwann Cells ◽

Peripheral Nerve Regeneration ◽

Engineering Strategy

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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Genetically modified canine Schwann cells—In vitro and in vivo evaluation of their suitability for peripheral nerve tissue engineering

Journal of Neuroscience Methods ◽

10.1016/j.jneumeth.2009.11.023 ◽

2010 ◽

Vol 186 (2) ◽

pp. 202-208 ◽

Cited By ~ 21

Author(s):

Ruth Schmitte ◽

Andrea Tipold ◽

Veronika M. Stein ◽

Henning Schenk ◽

Cornelia Flieshardt ◽

...

Keyword(s):

Tissue Engineering ◽

Peripheral Nerve ◽

Schwann Cells ◽

Genetically Modified ◽

Nerve Tissue ◽

In Vivo Evaluation ◽

Nerve Tissue Engineering

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Retroviral labeling of Schwann cells: In vitro characterization and in vivo transplantation to improve peripheral nerve regeneration

Glia ◽

10.1002/glia.1035 ◽

2001 ◽

Vol 34 (1) ◽

pp. 8-17 ◽

Cited By ~ 121

Author(s):

Afshin Mosahebi ◽

Barbara Woodward ◽

Mikael Wiberg ◽

Robin Martin ◽

Giorgio Terenghi

Keyword(s):

Peripheral Nerve ◽

Nerve Regeneration ◽

Schwann Cells ◽

Peripheral Nerve Regeneration ◽

In Vitro Characterization

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Upregulated lncARAT in Schwann Cells Promotes Axonal Regeneration through Recruiting Macrophages and Inducing Macrophages M2 Polarization

10.21203/rs.3.rs-543511/v1 ◽

2021 ◽

Author(s):

Gang Yin ◽

Yaofa Lin ◽

Peilin Wang ◽

Jun Zhou ◽

Haodong Lin

Keyword(s):

Peripheral Nerve ◽

Schwann Cells ◽

Axonal Regeneration ◽

Noncoding Rna ◽

Macrophage Polarization ◽

Nerve Repair ◽

M2 Polarization ◽

Sciatic Nerves

Abstract Background: Axonal regeneration following peripheral nerve injury largely depends on a favorable microenvironment. Schwann cells (SCs) play a crucial role in axonal regeneration by interacting with macrophages, but the mechanisms underlying macrophages recruitment and polarization remain unclear. Methods: The total RNA of crushed sciatic nerves and intact contralateral nerves was extracted and used to RNA-sequencing (RNA-seq). The differentially expressed long noncoding RNA (lncRNA) and mRNAs were analyzed using bioinformatics analysis, and were verified using qPCR and western blot analysis. The putative role of lncRNA in nerve regeneration was analyzed in vitro and in vivo. Macrophage polarization phenotype was identified by assessing IL-10, Arg-1, and CD206.Results: Here we identified an lncRNA, termed Axon Regeneration-Associated Transcript (lncARAT), upregulated in SCs and SCs-derived exosomes after crushed sciatic nerves (CSN). LncARAT contributed to axonal regeneration and improved motor functional recovery. Mechanistically, lncARAT epigenetically activated CCL2 expression by recruiting KMT2A to CCL2 promoter, which resulted in an increased H3K4 trimethylation and CCL2 transcription in SCs. CCL2 upregulation facilitated the infiltration of macrophages into the injured nerves. Meanwhile, lncARAT-enriched exosomes were released from SCs and incorporated into macrophages. Once in macrophage, lncARAT functioned as an endogenous sponge to adsorb miRNA-329-5p, resulting in an increased SOCS2 expression, which facilitated macrophage M2 polarization through a STAT1/6-dependent pathway, thus promoted axonal regeneration. Conclusions: LncARAT may serve as a promising therapeutic avenue for peripheral nerve repair.

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Pleiotrophin Cellular Localization in Nerve Regeneration after Peripheral Nerve Injury

Journal of Histochemistry & Cytochemistry ◽

10.1369/jhc.4a6574.2005 ◽

2005 ◽

Vol 53 (8) ◽

pp. 971-977 ◽

Cited By ~ 31

Author(s):

Brigitte Blondet ◽

Gilles Carpentier ◽

Fouad Lafdil ◽

Jose Courty

Keyword(s):

Endothelial Cells ◽

Peripheral Nerve ◽

Nerve Regeneration ◽

Schwann Cells ◽

Nerve Injury ◽

Peripheral Nerve Injury ◽

Cellular Localization ◽

Heparin Binding

Pleiotrophin (PTN) is a member of the family of heparin-binding growth factors that displays mitogenic activities and promotes neurite outgrowth in vitro. In vivo, PTN is widely expressed along pathways of developing axons during the late embryonic and early postnatal period. Although the level of PTN gene expression is very low during adulthood, activation of the gene may occur during recovery from injury and seems to play an important role in tissue regeneration processes. In this study, we investigated whether PTN was involved in the regenerative process of injured peripheral nerves. To refer localization of the fluorescent markers to myelinated axons, we developed a specific computer tool for colocalization of fluorescence images with phase contrast images. Immunohistochemical analysis showed PTN in different types of nonneural cells in distal nerve segments, including Schwann cells, macrophages, and endothelial cells, but not in axons. Schwann cells exhibited PTN immunoreactivity as early as 2 days after injury, whereas PTN-positive macrophages were found 1 week later. Strong PTN immunoreactivity was noted in endothelial cells at all time points. These findings support the idea that PTN participates in the adaptive response to peripheral nerve injury. A better understanding of its contribution may suggest new strategies for enhancing peripheral nerve regeneration.

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Interleukin-4 Regulates the Expression of CD209 and Subsequent Uptake of Mycobacterium leprae by Schwann Cells in Human Leprosy

Infection and Immunity ◽

10.1128/iai.00454-10 ◽

2010 ◽

Vol 78 (11) ◽

pp. 4634-4643 ◽

Cited By ~ 20

Author(s):

Rosane M. B. Teles ◽

Stephan R. Krutzik ◽

Maria T. Ochoa ◽

Rosane B. Oliveira ◽

Euzenir N. Sarno ◽

...

Keyword(s):

Schwann Cell ◽

Peripheral Nerve ◽

Schwann Cells ◽

Primary Cultures ◽

Mycobacterium Leprae ◽

Microbial Pathogens ◽

Interleukin 4 ◽

Common Mechanism ◽

Specific Cell

ABSTRACT The ability of microbial pathogens to target specific cell types is a key aspect of the pathogenesis of infectious disease. Mycobacterium leprae, by infecting Schwann cells, contributes to nerve injury in patients with leprosy. Here, we investigated mechanisms of host-pathogen interaction in the peripheral nerve lesions of leprosy. We found that the expression of the C-type lectin, CD209, known to be expressed on tissue macrophages and to mediate the uptake of M. leprae, was present on Schwann cells, colocalizing with the Schwann cell marker, CNPase (2′,3′-cyclic nucleotide 3′-phosphodiesterase), along with the M. leprae antigen PGL-1 in the peripheral nerve biopsy specimens. In vitro, human CD209-positive Schwann cells, both from primary cultures and a long-term line, have a higher binding of M. leprae compared to CD209-negative Schwann cells. Interleukin-4, known to be expressed in skin lesions from multibacillary patients, increased CD209 expression on human Schwann cells and subsequent Schwann cell binding to M. leprae, whereas Th1 cytokines did not induce CD209 expression on these cells. Therefore, the regulated expression of CD209 represents a common mechanism by which Schwann cells and macrophages bind and take up M. leprae, contributing to the pathogenesis of leprosy.

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The neural crest population responding to endothelin-3 in vitro includes multipotent cells

Journal of Cell Science ◽

10.1242/jcs.110.14.1673 ◽

1997 ◽

Vol 110 (14) ◽

pp. 1673-1682 ◽

Cited By ~ 1

Author(s):

J.G. Stone ◽

L.I. Spirling ◽

M.K. Richardson

Keyword(s):

Neural Crest ◽

Schwann Cells ◽

Cell Types ◽

Developmental Potential ◽

Colony Assay ◽

Cellular Targets ◽

Multipotent Cells ◽

Endothelin 3

The peptide endothelin 3 (EDN3) is essential for normal neural crest development in vivo, and is a potent mitogen for quail truncal crest cells in vitro. It is not known which subpopulations of crest cells are targets for this response, although it has been suggested that EDN3 is selective for melanoblasts. In the absence of cell markers for different precursor types in the quail crest, we have characterised EDN3-responsive cell types using in vitro colony assay and clonal analysis. Colonies were analysed for the presence of Schwann cells, melanocytes, adrenergic cells or sensory-like cells. We provide for the first time a description of the temporal pattern of lineage segregation in neural crest cultures. In the absence of exogenous EDN3, crest cells proliferate and then differentiate. Colony assay indicates that in these differentiated cultures few undifferentiated precursors remain and there is a low replating efficiency. By contrast, in the presence of 100 ng/ml EDN3 differentiation is inhibited and most of the cells maintain the ability to give rise to mixed colonies and clones containing neural crest derivatives. A high replating efficiency is maintained. In secondary culture there was a progressive decline in the number of cell types per colony in control medium. This loss of developmental potential was not seen when exogenous EDN3 was present. Cell type analysis suggests two novel cellular targets for EDN3 under these conditions. Contrary to expectations, one is a multipotent precursor whose descendants include melanocytes, adrenergic cells and sensory-like cells; the other can give rise to melanocytes and Schwann cells. Our data do not support previous claims that the action of EDN3 in neural crest culture is selective for cells in the melanocyte lineage.

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