Evidence map›Paper›PMID 36647161›Full record

ArticleBiomaterials research2023

Engineered exosomes enriched in netrin-1 modRNA promote axonal growth in spinal cord injury by attenuating inflammation and pyroptosis.

Xiao Lu, Guangyu Xu, Zhidi Lin, Fei Zou, Siyang Liu, Yuxuan Zhang, Wei Fu, Jianyuan Jiang, Xiaosheng Ma, Jian Song

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biomaterials research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed, 2 pooled it
10.5field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

46 citing papers in PubMed, 2 syntheses or guidelines pooled it, 68 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 1 country.

Xiao Lu *Department of Orthopedics, Huashan Hospital, Fudan University, No. 12, Middle Wulumuqi Road, Jing'an District, Shanghai, 200040, China.
Guangyu Xu *Department of Orthopedics, Huashan Hospital, Fudan University, No. 12, Middle Wulumuqi Road, Jing'an District, Shanghai, 200040, China.
Zhidi Lin *Department of Orthopedics, Huashan Hospital, Fudan University, No. 12, Middle Wulumuqi Road, Jing'an District, Shanghai, 200040, China.
Fei Zou *Department of Orthopedics, Huashan Hospital, Fudan University, No. 12, Middle Wulumuqi Road, Jing'an District, Shanghai, 200040, China.
Siyang LiuDepartment of Orthopedics, Huashan Hospital, Fudan University, No. 12, Middle Wulumuqi Road, Jing'an District, Shanghai, 200040, China.
Yuxuan ZhangDepartment of Orthopedics, Huashan Hospital, Fudan University, No. 12, Middle Wulumuqi Road, Jing'an District, Shanghai, 200040, China.
Wei FuInstitute of Pediatric Translational Medicine, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China. fuweizhulu@163.com.
Jianyuan JiangDepartment of Orthopedics, Huashan Hospital, Fudan University, No. 12, Middle Wulumuqi Road, Jing'an District, Shanghai, 200040, China. jianyuanjiang@sina.com.
Xiaosheng MaDepartment of Orthopedics, Huashan Hospital, Fudan University, No. 12, Middle Wulumuqi Road, Jing'an District, Shanghai, 200040, China. mxshs893@126.com.
Jian SongDepartment of Orthopedics, Huashan Hospital, Fudan University, No. 12, Middle Wulumuqi Road, Jing'an District, Shanghai, 200040, China. jsong16@fudan.edu.cn.
Fudan University · CNHuashan Hospital · CNShanghai Children's Medical Center · CN

Funding

National Natural Science Foundation of China 82102620, 82072488, 81871552, 82272549, 81972093Shanghai Sailing Program 20YF1429900Young Health Talents of Shanghai Municipal Health Commission 2022YQ011
6 · The paper itself

Abstract

backgroundSpinal cord injury (SCI) brings a heavy burden to individuals and society, and there is no effective treatment at present. Exosomes (EX) are cell secreted vesicles containing molecules such as nucleic acids and proteins, which hold promise for the treatment of SCI. Netrin-1 is an axon guidance factor that regulates neuronal growth. We investigated the effects of engineered EX enriched in netrin-1 chemically synthetic modified message RNA (modRNA) in treating SCI in an attempt to find a novel therapeutic approach for SCI.

methodsNetrin-1 modRNA was transfected into bone marrow mesenchymal stem cells to obtain EX enriched with netrin-1 (EX-netrin1). We built an inflammatory model in vitro with lipopolysaccharide (LPS) in vitro to study the therapeutic effect of EX-netrin1 on SCI. For experiments in vitro, ELISA, CCK-8 assay, immunofluorescence staining, lactate dehydrogenase release experiments test, real-time quantitative polymerase chain reaction, and western blot were conducted. At the same time, we constructed a rat model of SCI. MRI, hematoxylin-eosin and Nissl staining were used to assess the extent of SCI in rats.

resultsIn vitro experiments showed that EX had no effect on the viability of oligodendrocytes and PC12 cells. EX-netrin1 could attenuate LPS-induced inflammation and pyroptosis and accelerate axonal/dentritic growth in PC12 cells/oligodendrocytes. In addition, netrin-1 could activate the PI3K/AKT/mTOR signalling pathway upon binding to its receptor unc5b. When Unc5b and PI3K were inhibited, the effect of EX-netrin1 was weakened, which could be reversed by PI3K or mTOR activator. Our in vivo experiments indicated that EX-netrin1 could promote recovery in rats with SCI.

conclusionWe found that EX-netrin1 regulated inflammation, pyroptosis and axon growth in SCI via the Unc5b/PI3K/AKT/mTOR pathway, which provides a new strategy for the treatment of SCI.

Indexed as

Engineered exosomesmodRNANetrin-1Spinal cord injuryUnc5b/PI3K/AKT/mTOR

Identifiers

PMID36647161
PMCPMC9843879
OpenAlexW4316653380

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.