Functional Screening and Biosafety Identify of the Potential Application of Let-7a in Injured Peripheral Nerve Regeneration

Author(s):  
Qianqian Chen ◽  
Qianyan Liu ◽  
Pan Wang ◽  
Tianmei Qian ◽  
Xinghui Wang ◽  
...  

Abstract Proper supporting factor can possess the ability to enhance neuron regeneration, for instance, neurotrophic effects especially nerve growth factor (NGF). However, the in vivo applications of NGF are largely limited by its intrinsic disadvantages. Considering that let-7 targets and regulates NGF, and let-7 is also the core and harbor regulators in peripheral nerve repair and regeneration, we evaluated the potential application in clinical. We firstly screened the let-7a as the most ideal let-7 family molecular by gene expression analysis and functional approach. We further evaluated the in vivo safety, the cell permeability of 3 main cells in regeneration micro-environment, and the morphological and functional indicators. Our study provides an essential basis for in vivo application of let-7 and pictured a vision for the clinical translation of miRNA as a prospective alternative for regenerative medicine.

2018 ◽  
Vol 6 (5) ◽  
pp. 1059-1075 ◽  
Author(s):  
C. R. Carvalho ◽  
S. Wrobel ◽  
C. Meyer ◽  
C. Brandenberger ◽  
I. F. Cengiz ◽  
...  

This experimental work considers the innovative use of the biomaterial Gellan Gum (GG) as a luminal filler for nerve guidance channels.


Nanomedicine ◽  
2019 ◽  
Vol 14 (20) ◽  
pp. 2659-2677 ◽  
Author(s):  
Igor D Luzhansky ◽  
Leland C Sudlow ◽  
David M Brogan ◽  
Matthew D Wood ◽  
Mikhail Y Berezin

Surgical intervention followed by physical therapy remains the major way to repair damaged nerves and restore function. Imaging constitutes promising, yet underutilized, approaches to improve surgical and postoperative techniques. Dedicated methods for imaging nerve regeneration will potentially provide surgical guidance, enable recovery monitoring and postrepair intervention, elucidate failure mechanisms and optimize preclinical procedures. Herein, we present an outline of promising innovations in imaging-based tracking of in vivo peripheral nerve regeneration. We emphasize optical imaging because of its cost, versatility, relatively low toxicity and sensitivity. We discuss the use of targeted probes and contrast agents (small molecules and nanoparticles) to facilitate nerve regeneration imaging and the engineering of grafts that could be used to track nerve repair. We also discuss how new imaging methods might overcome the most significant challenges in nerve injury treatment.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Tamara Weiss ◽  
Sabine Taschner-Mandl ◽  
Lukas Janker ◽  
Andrea Bileck ◽  
Fikret Rifatbegovic ◽  
...  

AbstractAdult Schwann cells (SCs) possess an inherent plastic potential. This plasticity allows SCs to acquire repair-specific functions essential for peripheral nerve regeneration. Here, we investigate whether stromal SCs in benign-behaving peripheral neuroblastic tumors adopt a similar cellular state. We profile ganglioneuromas and neuroblastomas, rich and poor in SC stroma, respectively, and peripheral nerves after injury, rich in repair SCs. Indeed, stromal SCs in ganglioneuromas and repair SCs share the expression of nerve repair-associated genes. Neuroblastoma cells, derived from aggressive tumors, respond to primary repair-related SCs and their secretome with increased neuronal differentiation and reduced proliferation. Within the pool of secreted stromal and repair SC factors, we identify EGFL8, a matricellular protein with so far undescribed function, to act as neuritogen and to rewire cellular signaling by activating kinases involved in neurogenesis. In summary, we report that human SCs undergo a similar adaptive response in two patho-physiologically distinct situations, peripheral nerve injury and tumor development.


2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Feixiang Chen ◽  
Weihuang Liu ◽  
Qiang Zhang ◽  
Ping Wu ◽  
Ao Xiao ◽  
...  

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.


2016 ◽  
Vol 11 (3) ◽  
pp. 508 ◽  
Author(s):  
Qi-shun Huang ◽  
A-chao Han ◽  
Jing-xiu Deng ◽  
Huai-yuan Zheng ◽  
Pan Zhou ◽  
...  

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