Extracellular Environment-Controlled Angiogenesis, and Potential Application for Peripheral Nerve Regeneration

Saio, Shingo; Konishi, Kanna; Hitomi, Hirofumi; Tamura, Yuki; Masutani, Teruaki; Iddamalgoda, Arunasiri; Ichihashi, Masamitsu; Hasegawa, Hiroshi; Mizutani, Ken-ichi

doi:10.3390/ijms222011169

Cited by 26 publications

(18 citation statements)

References 63 publications

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“…[ 59 ] A rapid remodeling of damaged blood vessels provides not only support and assurance for the nutrient supply of nerve cells in the conduit, but also a “track” for SCs migration and axon growth. [ 60 ] It has been shown that EVs from different cell types showed stimulatory or inhibitory effects on angiogenesis, which are highly dependent on the EV content and surface molecule expression. The EVs generated in response to interleukin‐3 stimulation were able to promote angiogenesis through transfer of miR‐126‐3p and pSTAT5 into the recipient endothelial cells, leading to a lower Spred‐1 level and increased ERK1/2 activation and cyclin D1 transcription.…”

Section: Discussionmentioning

confidence: 99%

A Novel Superparamagnetic Multifunctional Nerve Scaffold: A Remote Actuation Strategy to Boost In Situ Extracellular Vesicles Production for Enhanced Peripheral Nerve Repair

Xia,

Gao,

Qian

et al. 2023

Advanced Materials

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Extracellular vesicles (EVs) have inherent advantages over cell‐based therapies in regenerative medicine because their cargos of abundant bioactive cues. Several strategies are proposed to tune EVs production in vitro. However, it remains a challenge for manipulation of EVs production in vivo, which poses significant difficulties for EVs‐based therapies that aim to promote tissue regeneration, particularly for long‐term treatment of diseases like peripheral neuropathy. Herein, a superparamagnetic nanocomposite scaffold capable of controlling EVs production on‐demand is constructed by incorporating polyethyleneglycol/polyethyleneimine modified superparamagnetic nanoparticles into polyacrylamide/hyaluronic acid double‐network hydrogel (Mag‐gel). The Mag‐gel is highly sensitive to rotating magnetic field (RMF), and could act as mechano‐stimulative platform to exert micro/nano‐scale forces on encapsulated Schwann cells (SCs), an essential glial cell in supporting nerve regeneration. By switching the ON/OFF state of RMF, the Mag‐gel could scale up local production of SCs‐derived EVs (SCs‐EVs) both in vitro and in vivo. Further transcriptome sequencing indicated an enrichment of transcripts favorable in axon growth, angiogenesis, and inflammatory regulation of SCs‐EVs in Mag‐gel with RMF, which ultimately results in optimized nerve repair in vivo. Overall, our research provides a noninvasive and remotely time‐scheduled method for fine‐tuning EVs‐based therapies to accelerate tissue regeneration, including that of peripheral nerves.This article is protected by copyright. All rights reserved

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Section: Discussionmentioning

confidence: 99%

A Novel Superparamagnetic Multifunctional Nerve Scaffold: A Remote Actuation Strategy to Boost In Situ Extracellular Vesicles Production for Enhanced Peripheral Nerve Repair

Xia,

Gao,

Qian

et al. 2023

Advanced Materials

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“…It promotes axonal growth, provides essential cues for axonal sprouting, and directs axonal regeneration toward their target, facilitating functional recovery [31,32] . VEGF is a potent angiogenic factor that plays a critical role in angiogenesis, which is essential for the revascularization of regenerating nerves [33] . VEGF exhibits direct neuroprotective effects on neurons [34] and enhances SC proliferation and migration after peripheral nerve injury [35] .…”

Section: Discussionmentioning

confidence: 99%

Mechanism of Wharton's Jelly-derived mesenchymal stem cells in promoting peripheral nerve regeneration

Shin,

Choi,

Kim

2023

Preprint

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Warton’s jelly-derived MSCs (WJ-MSCs) play key roles to improving nerve regeneration in acellular nerve grafts (ANGs), however the mechanism of WJ-MSCs releted nerve regeneration remain unclear. This study investigated how WJ-MSCs contribute to peripheral nerve regeneration by examining immunomodulatory and paracrine effects, and differentiation potential. WJ-MSCs were isolated from umbilical cords. ANGs (control) or WJ-MSC-loaded ANGs (WJ-MSCs group) were transplanted in injury animal model. Functional recovery was evaluated by ankle angle and tetanic force measurements up to 16 weeks post-surgery. Tissue biopsies at 3, 7, and 14 days post-transplantation were used to analyze macrophage markers and interleukin (IL) levels, paracrine effects, and MSC differentiation potential by quantitative real-time polymerase chain reaction (RT-qPCR) and immunofluorescence staining. The WJ-MSCs group showed significantly higher ankle angle at 4 weeks and higher isometric tetanic force at 16 weeks, and increased expression of CD206 and IL10 at 7 or 14 days than the control group. Increased levels of neurotrophic and vascular growth factors were observed at 14 days. The WJ-MSCs group showed higher expression levels of S100β; however, the co-staining of human nuclei was faint. This study demonstrates that WJ-MSCs' immunomodulation and paracrine actions contribute to peripheral nerve regeneration more than their differentiation potential.

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“…The conductive MXene-PCL NGC matched well with the electrophysiological properties of the sciatic nerve; meanwhile, a higher signal of CD34 and CD31 indicated the electrical signals could stimulate neovascularization. In turn, the vascular would strengthen the nutritional supply for neural functional reconstruction ( Saio et al, 2021 ; Thibodeau et al, 2021 ; Wu et al, 2021 ; Xiaobin Li et al, 2021 ). The conductive MXene NGC showed a better effect in nerve regeneration than nonconductive NGC.…”

Section: Discussionmentioning

confidence: 99%

Ti3C2Tx MXene-Coated Electrospun PCL Conduits for Enhancing Neurite Regeneration and Angiogenesis

Nan

Lin

Wang

et al. 2022

Front. Bioeng. Biotechnol.

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An electrical signal is the key basis of normal physiological function of the nerve, and the stimulation of the electric signal also plays a very special role in the repair process of nerve injury. Electric stimulation is shown to be effective in promoting axonal regeneration and myelination, thereby promoting nerve injury repair. At present, it is considered that electric conduction recovery is a key aspect of regeneration and repair of long nerve defects. Conductive neural scaffolds have attracted more and more attention due to their similar electrical properties and good biocompatibility with normal nerves. Herein, PCL and MXene-PCL nerve guidance conduits (NGCs) were prepared; their effect on nerve regeneration was evaluated in vitro and in vivo. The results show that the NGCs have good biocompatibility in vitro. Furthermore, a sciatic nerve defect model (15 mm) of SD rats was made, and then the fabricated NGCs were implanted. MXene-PCL NGCs show similar results with the autograft in the sciatic function index, electrophysiological examination, angiogenesis, and morphological nerve regeneration. It is possible that the conductive MXene-PCL NGC could transmit physiological neural electric signals, induce angiogenesis, and stimulate nerve regeneration. This paper presents a novel design of MXene-PCL NGC that could transmit self-originated electric stimulation. In the future, it can be combined with other features to promote nerve regeneration.

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Extracellular Environment-Controlled Angiogenesis, and Potential Application for Peripheral Nerve Regeneration

Cited by 26 publications

References 63 publications

A Novel Superparamagnetic Multifunctional Nerve Scaffold: A Remote Actuation Strategy to Boost In Situ Extracellular Vesicles Production for Enhanced Peripheral Nerve Repair

A Novel Superparamagnetic Multifunctional Nerve Scaffold: A Remote Actuation Strategy to Boost In Situ Extracellular Vesicles Production for Enhanced Peripheral Nerve Repair

Mechanism of Wharton's Jelly-derived mesenchymal stem cells in promoting peripheral nerve regeneration

Ti3C2Tx MXene-Coated Electrospun PCL Conduits for Enhancing Neurite Regeneration and Angiogenesis

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