scholarly journals Peripheral Nerve Repair with Cultured Schwann Cells: Getting Closer to the Clinics

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Maria Carolina O. Rodrigues ◽  
Antonio Antunes Rodrigues ◽  
Loren E. Glover ◽  
Julio Voltarelli ◽  
Cesario V. Borlongan
Keyword(s):  
Bone Marrow ◽  
Peripheral Nerve ◽  
Schwann Cells ◽  
Nerve Repair ◽  
Experimental Studies ◽  
Experimental Treatment ◽  
Mesenchymal Cells ◽  
Nerve Conduits ◽  
Cultured Schwann Cells

Peripheral nerve injuries are a frequent and disabling condition, which affects 13 to 23 per 100.000 persons each year. Severe cases, with structural disruption of the nerve, are associated with poor functional recovery. The experimental treatment using nerve grafts to replace damaged or shortened axons is limited by technical difficulties, invasiveness, and mediocre results. Other therapeutic choices include the adjunctive application of cultured Schwann cells and nerve conduits to guide axonal growth. The bone marrow is a rich source of mesenchymal cells, which can be differentiatedin vitrointo Schwann cells and subsequently engrafted into the damaged nerve. Alternatively, undifferentiated bone marrow mesenchymal cells can be associated with nerve conduits and afterward transplanted. Experimental studies provide evidence of functional, histological, and electromyographical improvement following transplantation of bone-marrow-derived cells in animal models of peripheral nerve injury. This paper focuses on this new therapeutic approach highlighting its direct translational and clinical utility in promoting regeneration of not only acute but perhaps also chronic cases of peripheral nerve damage.

scholarly journals Electrospun Hyaluronan-Gelatin Nanofibrous Matrix for Nerve Tissue Engineering

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Hau-Min Liou ◽  
Lih-Rou Rau ◽  
Chun-Chiang Huang ◽  
Meng-Ru Lu ◽  
Fu-Yin Hsu
Keyword(s):  
Peripheral Nerve ◽  
Schwann Cells ◽  
Cell Attachment ◽  
Nerve Repair ◽  
Critical Role ◽  
Nerve Tissue ◽  
Growth Environment ◽  
Biological Performance ◽  
Electrospun Gelatin

Schwann cells play a critical role in the repair of the peripheral nerve. The goal of this study was to fabricate electrospun gelatin (Gel) and hyaluronan-gelatin (HA-Gel) composite nanofibers to provide a suitable growth environment for Schwann cells. The fiber diameters of Gel, 0.5 HA-Gel, 1 HA-Gel, and 1.5 HA-Gel were 130 ± 30 nm, 294 ± 87 nm, 362 ± 129 nm, and 224 ± 54 nm, respectively. The biological performance of Gel and HA-Gel was evaluated using anin vitroculture of RT4-D6P2T rat Schwann cells. We found that the cell attachment and proliferation rates were not significantly different on these matrices. However, the Schwann cells displayed better organized F-actin on HA-Gel than on Gel. Moreover, the expression levels of several genes, including Nrg1, GFAP, and P0, were significantly higher on HA-Gel than on Gel. In addition, the levels of Nrg1 and P0 protein expression were also higher on the HA-Gel than on Gel. These results indicate that the hyaluronan-gelatin composite nanofibrous matrix could potentially be used in peripheral nerve repair.

GELATIN-TRICALCIUM PHOSPHATE MEMBRANE MODIFIED WITH NGF AND CULTURED SCHWANN CELLS FOR PERIPHERAL NERVE REPAIR: A TISSUE ENGINEERING APPROACH

2006 ◽  
Vol 18 (02) ◽  
pp. 47-54 ◽  
Author(s):  
MING-HONG CHEN ◽  
PEI-RU CHEN ◽  
MEI-HSIU CHEN ◽  
SUNG-TSANG HSIEH ◽  
JING-SHAN HUANG ◽  
...  
Keyword(s):  
Growth Factors ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Schwann Cells ◽  
Tricalcium Phosphate ◽  
Nerve Repair ◽  
Peripheral Nerve Regeneration ◽  
Nerve Growth ◽  
Nerve Growth Factors ◽  
Cultured Schwann Cells

This study attempted to enhance the efficacy of peripheral nerve regeneration using our previously developed gelatin-tricalcium phosphate (GTG) conduits by incorporating them with nerve growth factors and cultured Schwann cells. The nerve growth factors were covalently immobilized onto the GTG conduits (GEN) using carbodiimide. Schwann cells were harvested from neonatal Lewis rats, cultured for seven days and injected into the GEN conduits. The experiment was performed in three groups: GTG conduits, GEN conduits and GEN conduits with Schwann cells injected (GEN+Sc). The effects of different conduits (GTG, GEN and GEN with Schwann cells) on the peripheral nerve regeneration were evaluated in rat sciatic nerve repair model. 24 weeks after implantation of conduits, degradation of the conduits in all groups was illustrated by the fragmentation of the conduits. All conduits were well tolerated by the host tissue. Under microscopic evaluations, regenerated nerve tissue with myelinated and unmyelinated axons presented in all groups. Histomorphometrically, the total nerve area of GEN+Sc group was significantly higher than GTG group. Conversely, the autotomy score evaluated 12 weeks after nerve repair showed better results for GTG group. Besides, GEN+Sc group had the highest average recovery index of compound muscle action potential, but the difference among each group did not reach statistical significance. Although the electrophysiological recovery of nerve was not significantly improved with GEN+Sc conduit, nerve repair using tissue engineered conduits still provided better histological results. However, it should be noticed that autotomy may be the price paid for enhanced peripheral nerve.

scholarly journals Material advancement in tissue-engineered nerve conduit

2021 ◽  
Vol 10 (1) ◽  
pp. 488-503
Author(s):  
Wufei Dai ◽  
Yating Yang ◽  
Yumin Yang ◽  
Wei Liu
Keyword(s):  
Peripheral Nerve ◽  
Animal Studies ◽  
Nerve Repair ◽  
Donor Site ◽  
Life Quality ◽  
Nerve Grafts ◽  
Synthetic Materials ◽  
Nerve Conduits ◽  
Extracellular Matrix Components

Abstract Peripheral nerve injuries resulting from various traumatic events can cause mobility problems and sensory impairment, jeopardizing patients’ life quality and bringing serious economic burdens. Due to the shortcomings of autologous nerve grafts, such as limited tissue sources, unmatched size, and loss of innervation at the donor site, tissue-engineered nerve grafts using both natural and synthetic materials have been employed in the treatment of peripheral nerve defect and to promote nerve regeneration. Apart from traditional advantages such as good biocompatibility and controllable degradation, the development of fabrication technology and the advancement in material science have endowed tissue-engineered nerve conduits with upgraded properties such as biomimetic surface topography, extracellular matrix components, neurotrophic factors, and cell seeding, or a conduit with micropores on the surface for substance exchange and/or with fillers inside for microenvironment simulation. This article reviews recent progress in the biomaterials employed in fabricating tissue-engineered nerve conduits, in vitro characterization, and their applications in nerve repair in animal studies as well as in clinical trials.

scholarly journals The Use of Degradable Nerve Conduits for Human Nerve Repair: A Review of the Literature

2005 ◽  
Vol 2 (1) ◽  
pp. 39-43 ◽  
Author(s):  
M. F. Meek ◽  
K. Jansen ◽  
P. H. Robinson
Keyword(s):  
Peripheral Nerve ◽  
Peripheral Nerves ◽  
Nerve Repair ◽  
Experimental Studies ◽  
Review Of The Literature ◽  
Nerve Grafts ◽  
Nerve Guides ◽  
Clinical Challenge ◽  
Nerve Conduits ◽  
Human Nerve

The management of peripheral nerve injury continues to be a major clinical challenge. The most widely used technique for bridging defects in peripheral nerves is the use of autologous nerve grafts. This technique, however, has some disadvantages. Many alternative experimental techniques have thus been developed, such as degradable nerve conduits. Degradable nerve guides have been extensively studied in animal experimental studies. However, the repair of human nerves by degradable nerve conduits has been limited to only a few clinical studies. In this paper, an overview of the available international published literature on degradable nerve conduits for bridging human peripheral nerve defects is presented for literature available until 2004. Also, the philosophy on the use of nerve guides and nerve grafts is given.

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

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.

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

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.

scholarly journals IL-17F depletion accelerates chitosan conduit guided peripheral nerve regeneration

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Feixiang Chen ◽  
Weihuang Liu ◽  
Qiang Zhang ◽  
Ping Wu ◽  
Ao Xiao ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Knockout Mice ◽  
Inflammatory Markers ◽  
Nerve Repair ◽  
Peripheral Nerve Regeneration ◽  
Wild Type ◽  
Anti Inflammatory

AbstractPeripheral nerve injury is a serious health problem and repairing long nerve deficits remains a clinical challenge nowadays. Nerve guidance conduit (NGC) serves as the most promising alternative therapy strategy to autografts but its repairing efficiency needs improvement. In this study, we investigated whether modulating the immune microenvironment by Interleukin-17F (IL-17F) could promote NGC mediated peripheral nerve repair. Chitosan conduits were used to bridge sciatic nerve defect in IL-17F knockout mice and wild-type mice with autografts as controls. Our data revealed that IL-17F knockout mice had improved functional recovery and axonal regeneration of sciatic nerve bridged by chitosan conduits comparing to the wild-type mice. Notably, IL-17F knockout mice had enhanced anti-inflammatory macrophages in the NGC repairing microenvironment. In vitro data revealed that IL-17F knockout peritoneal and bone marrow derived macrophages had increased anti-inflammatory markers after treatment with the extracts from chitosan conduits, while higher pro-inflammatory markers were detected in the Raw264.7 macrophage cell line, wild-type peritoneal and bone marrow derived macrophages after the same treatment. The biased anti-inflammatory phenotype of macrophages by IL-17F knockout probably contributed to the improved chitosan conduit guided sciatic nerve regeneration. Additionally, IL-17F could enhance pro-inflammatory factors production in Raw264.7 cells and wild-type peritoneal macrophages. Altogether, IL-17F may partially mediate chitosan conduit induced pro-inflammatory polarization of macrophages during nerve repair. These results not only revealed a role of IL-17F in macrophage function, but also provided a unique and promising target, IL-17F, to modulate the microenvironment and enhance the peripheral nerve regeneration.

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

2010 ◽  
Vol 78 (11) ◽  
pp. 4634-4643 ◽  
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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