Human umbilical cord mesenchymal stem cell-derived exosomes combined with mouse nerve growth factor can more effectively ameliorate the motor disorder and brain pathological injury in mice with cerebral palsy.

IF 2.1 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL
Xingxing Chen, Yipa Sai, Weijing Cui, Xiaoxia Hu, Jing Liu, Xiaofeng Cao, Shili Wu
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引用次数: 0

Abstract

Background: Cerebral palsy (CP) is a neurodevelopmental disorder and motor disorder syndrome. It has been confirmed that mesenchymal stem cells (MSCs) and mouse nerve growth factor (mNGF) can repair brain tissue damage and nerve injury; however, exosomes derived from healthy cells may have a comparable therapeutic potential as the cells themselves.

Objectives: The purpose of this study was to explore the improvement effect of human umbilical cord mesenchymal stem cell (hUC-MSCs)-derived exosomes on a CP model and determine whether there is a synergistic effect when combined with mNGF.

Material and methods: Exosomes were isolated from hUC-MSCs and examined using transmission electron microscopy (TEM), particle size and western blot (WB). A total of 38 BALB/c mice (male, postnatal day 6 (PND6)) were randomly divided into 5 groups: sham group, CP group, CP-exo group, CP-mNGF group, and CP-exo-mNGF group. Hypoxic induction after unilateral common carotid artery ligation combined with lipopolysaccharide (LPS) infection was used to construct the CP model. Pathological damage to neuron tissue and synaptic structures in the hippocampus was confirmed using light microscopy after hematoxylin-eosin (H&E) staining and TEM, respectively. Survival of neurons was evaluated using Nissl staining. Western blot was applied to monitor PSD-95 and synaptophysin (SYN) protein levels.

Results: This study indicated that exosomes released by hUC-MSCs ameliorated brain damage and synaptic structure destruction in CP mice induced by hypoxic ischemia and LPS infection. When combined with mNGF, there was more effective improvement. In the CP group, neuronal function was severely impaired; however, hUC-MSCs-derived exosomes and mNGF improved it. PSD-95 and SYN proteins were presynaptic and postsynaptic proteins, respectively. Interestingly, the PSD-95 and SYN protein levels were significantly lower in the CP mice, but with the addition of hUC-MSCs-exosomes or mNGF, they increased significantly, especially in the CP-exo-mNGF group.

Conclusions: The nerve function injury in CP can be improved the most when hUC-MSCs-derived exosomes are combined with mNGF through intraperitoneal (ip.) administration.

人脐带间充质干细胞外泌体联合小鼠神经生长因子能更有效地改善脑瘫小鼠的运动障碍和脑病理损伤。
背景:脑瘫(CP)是一种神经发育障碍和运动障碍综合征。已证实间充质干细胞(MSCs)和小鼠神经生长因子(mNGF)具有修复脑组织损伤和神经损伤的作用;然而,来自健康细胞的外泌体可能具有与细胞本身相当的治疗潜力。目的:本研究旨在探讨人脐带间充质干细胞(hUC-MSCs)来源的外泌体对CP模型的改善作用,并确定与mNGF联合使用是否有协同作用。材料和方法:从hUC-MSCs中分离外泌体,采用透射电镜(TEM)、颗粒大小和western blot (WB)检测。选取雄性、出生第6天(PND6) BALB/c小鼠38只,随机分为5组:sham组、CP组、CP-exo组、CP-exo- mngf组、CP-exo- mngf组。采用单侧颈总动脉结扎后缺氧诱导联合脂多糖(LPS)感染的方法建立CP模型。苏木精-伊红(H&E)染色和透射电镜分别观察海马神经元组织和突触结构的病理损伤。采用尼氏染色法观察神经元的存活情况。Western blot检测PSD-95和突触素(SYN)蛋白水平。结果:本研究表明hUC-MSCs释放的外泌体改善了缺氧缺血和LPS感染引起的CP小鼠脑损伤和突触结构破坏。当与mNGF联合使用时,改善效果更明显。CP组神经元功能严重受损;然而,huc - mscs衍生的外泌体和mNGF改善了它。PSD-95蛋白为突触前蛋白,SYN蛋白为突触后蛋白。有趣的是,PSD-95和SYN蛋白水平在CP小鼠中显著降低,但随着huc - mscs -外泌体或mNGF的加入,它们显著升高,尤其是在CP-exo-mNGF组。结论:huc - mscs来源的外泌体与mNGF联合腹腔给药可显著改善CP的神经功能损伤。
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来源期刊
Advances in Clinical and Experimental Medicine
Advances in Clinical and Experimental Medicine MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
3.70
自引率
4.80%
发文量
153
审稿时长
6-12 weeks
期刊介绍: Advances in Clinical and Experimental Medicine has been published by the Wroclaw Medical University since 1992. Establishing the medical journal was the idea of Prof. Bogumił Halawa, Chair of the Department of Cardiology, and was fully supported by the Rector of Wroclaw Medical University, Prof. Zbigniew Knapik. Prof. Halawa was also the first editor-in-chief, between 1992-1997. The journal, then entitled "Postępy Medycyny Klinicznej i Doświadczalnej", appeared quarterly. Prof. Leszek Paradowski was editor-in-chief from 1997-1999. In 1998 he initiated alterations in the profile and cover design of the journal which were accepted by the Editorial Board. The title was changed to Advances in Clinical and Experimental Medicine. Articles in English were welcomed. A number of outstanding representatives of medical science from Poland and abroad were invited to participate in the newly established International Editorial Staff. Prof. Antonina Harłozińska-Szmyrka was editor-in-chief in years 2000-2005, in years 2006-2007 once again prof. Leszek Paradowski and prof. Maria Podolak-Dawidziak was editor-in-chief in years 2008-2016. Since 2017 the editor-in chief is prof. Maciej Bagłaj. Since July 2005, original papers have been published only in English. Case reports are no longer accepted. The manuscripts are reviewed by two independent reviewers and a statistical reviewer, and English texts are proofread by a native speaker. The journal has been indexed in several databases: Scopus, Ulrich’sTM International Periodicals Directory, Index Copernicus and since 2007 in Thomson Reuters databases: Science Citation Index Expanded i Journal Citation Reports/Science Edition. In 2010 the journal obtained Impact Factor which is now 1.179 pts. Articles published in the journal are worth 15 points among Polish journals according to the Polish Committee for Scientific Research and 169.43 points according to the Index Copernicus. Since November 7, 2012, Advances in Clinical and Experimental Medicine has been indexed and included in National Library of Medicine’s MEDLINE database. English abstracts printed in the journal are included and searchable using PubMed http://www.ncbi.nlm.nih.gov/pubmed.
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