Identification of critical growth factors for peripheral nerve regeneration

ABSTRACTPeripheral nerve injuries (PNIs) can be most disabling, resulting in the loss of sensitivity, motor function and autonomic control in the involved anatomical segment. Although injured peripheral nerves are capable of regeneration, sub-optimal recovery of function is seen even with the best reconstruction. Distal axonal degeneration is an unavoidable consequence of PNI. There are currently few strategies aimed to maintain the distal pathway and/or target fidelity during regeneration across the zone of injury. The current state of the art approaches have been focussed on the site of nerve injury and not on their distal muscular targets or representative proximal cell bodies or central cortical regions. This is a comprehensive literature review of the neurochemistry of peripheral nerve regeneration and a state of the art analysis of experimental compounds (inorganic and organic agents) with demonstrated neurotherapeutic efficacy in improving cell body and neuron survival, reducing scar formation and maximising overall nerve regeneration.

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Development of heparin-conjugated nanofibers and a novel biological signal by immobilized growth factors for peripheral nerve regeneration

Journal of Bioscience and Bioengineering ◽

10.1016/j.jbiosc.2019.09.004 ◽

2020 ◽

Vol 129 (3) ◽

pp. 354-362 ◽

Cited By ~ 6

Author(s):

Yasuhiro Ikegami ◽

Hiroyuki Ijima

Keyword(s):

Growth Factors ◽

Peripheral Nerve ◽

Nerve Regeneration ◽

Peripheral Nerve Regeneration ◽

Biological Signal

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

Biomedical Engineering Applications Basis and Communications ◽

10.4015/s1016237206000105 ◽

2006 ◽

Vol 18 (02) ◽

pp. 47-54 ◽

Cited By ~ 2

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.

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

Cell Death and Disease ◽

10.1038/s41419-021-03706-8 ◽

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.

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Growth factors-based therapeutic strategies and their underlying signaling mechanisms for peripheral nerve regeneration

Acta Pharmacologica Sinica ◽

10.1038/s41401-019-0338-1 ◽

2020 ◽

Vol 41 (10) ◽

pp. 1289-1300 ◽

Cited By ~ 6

Author(s):

Rui Li ◽

Duo-hui Li ◽

Hong-yu Zhang ◽

Jian Wang ◽

Xiao-kun Li ◽

...

Keyword(s):

Growth Factors ◽

Peripheral Nerve ◽

Nerve Regeneration ◽

Biological Effects ◽

Peripheral Nerve Regeneration ◽

Complete Recovery ◽

Significant Loss ◽

Molecular Response ◽

Signaling Mechanisms ◽

Synthetic Materials

Abstract Peripheral nerve injury (PNI), one of the most common concerns following trauma, can result in a significant loss of sensory or motor function. Restoration of the injured nerves requires a complex cellular and molecular response to rebuild the functional axons so that they can accurately connect with their original targets. However, there is no optimized therapy for complete recovery after PNI. Supplementation with exogenous growth factors (GFs) is an emerging and versatile therapeutic strategy for promoting nerve regeneration and functional recovery. GFs activate the downstream targets of various signaling cascades through binding with their corresponding receptors to exert their multiple effects on neurorestoration and tissue regeneration. However, the simple administration of GFs is insufficient for reconstructing PNI due to their short half‑life and rapid deactivation in body fluids. To overcome these shortcomings, several nerve conduits derived from biological tissue or synthetic materials have been developed. Their good biocompatibility and biofunctionality made them a suitable vehicle for the delivery of multiple GFs to support peripheral nerve regeneration. After repairing nerve defects, the controlled release of GFs from the conduit structures is able to continuously improve axonal regeneration and functional outcome. Thus, therapies with growth factor (GF) delivery systems have received increasing attention in recent years. Here, we mainly review the therapeutic capacity of GFs and their incorporation into nerve guides for repairing PNI. In addition, the possible receptors and signaling mechanisms of the GF family exerting their biological effects are also emphasized.

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