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

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.

C-terminal domain small phosphatase 1 (CTDSP1) regulates growth factor expression and axonal regeneration

“…The site of injury contains a heterogeneous population of cells, and the increase in CTDSP1 after injury may therefore re ect the change in the type of cells that are present at the site of injury, such as the presence of injury-induced cells, like MPCs, which may express higher levels of CTDSP1 and lower levels of BDNF than muscle cells. Nevertheless, insu cient levels of BDNF and other neurotrophic factors at the site of injury are partly responsible for inhibition of axonal regeneration [5,28]. Importantly, our study suggests that it may be possible to increase the secretion of BDNF and other neurotrophic factors at the site of injury by modulating CTDSP1 activity.…”

“…Regeneration of peripheral nerves relies on the ability of peripheral neurons to switch to a regenerative state and on the development of a pro-regenerative environment at the site of injury created by local support cells. Both events require comprehensive transcriptional changes in both injured neurons and support cells [1][2][3][4]; however, therapeutic approaches have mainly focused on modulating or introducing a single or at most the combination of a limited number of molecules, rather than sustaining the regenerative program as a whole [5][6][7][8]. An overall epigenetic reprogramming approach could promote a favorable regenerative environment by targeting the support cells located at the site of injury, as well as activating the intrinsic mechanism of axonal regeneration in the neuronal cell bodies of the injured nerves located at a distance from the site of injury (Fig.…”

Biomimetic Approaches for Separated Regeneration of Sensory and Motor Fibers in Amputee People: Necessary Conditions for Functional Integration of Sensory–Motor Prostheses With the Peripheral Nerves

“…The first group includes five types of neurotrophic factors: axonal growth promoters (neurotrophins), neuropoietic cytokines, fibroblast growth factors, transforming growth factors, and insulin-like growth factors (Boyd and Gordon, 2003;Jin et al, 2009;Li et al, 2020).…”

“…Axonal growth promoters NGF, BDNF, NT3, NT4/5 Boyd and Gordon, 2003;Jin et al, 2009;Li et al, 2020 Transforming growth factors GDNF Allodi et al, 2012;Hoyng et al, 2014;Anand et al, 2017 Insulin-like growth factors IGF1 e IGF2 Di Giulio et al, 2000;Brushart et al, 2013 Fibroblast growth factors FGF2 Allodi et al, 2012;Brushart et al, 2013;Santos et al, 2016b Neuropoietic cytokines PTN, CNTF, IL6, LIF Mi et al, 2007;Gordon, 2014 Molecules integrated into the surrounding nerve tissue…”

Lesão Enegrecida-Azulada Em Mucosa Bucal: Possíveis Diagnósticos Diferenciais E Como Proceder

“…É possível observar perda da continuidade das fibras nervosas, reação inflamatória devido ao trauma ocorrido no local e formação de tecido cicatricial que dificulta a regeneração axonal. Nesse tipo de lesão o prognóstico espontâneo é negativo, necessitando assim na maioria das vezes de intervenção cirúrgica e a recuperação e regeneração são incompletas, não ocorrendo o reestabelecimento total das funções do nervo afetado(LI, 2020;LEUNG, 2019;SARIKOV;JUODZBALYS, 2014). tratamentos disponíveis para casos de parestesias podem trazer uma melhora nos sintomas, porém podem não alcançar uma recuperação completa.…”