Exosomes-Loaded Electroconductive Hydrogel Synergistically Promotes Tissue Repair after Spinal Cord Injury via Immunoregulation and Enhancement of Myelinated Axon Growth
机构:[1]School of Materials Science and Engineering and National Engineering, Research Center for Tissue Restoration and Reconstruction, South China University of Technology, No. 381, Wushan Road, Tianhe District, Guangzhou 510641, China[2]Department of Orthopedic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China浙江大学医学院附属第一医院[3]Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Medical Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 107, Yanjiang West Road, Yuexiu District, Guangzhou, Guangzhou 510120, China中山大学附属第二医院[4]Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, No. 1838, Guangzhou Avenue North, Baiyun District, Guangzhou, Guangdong 510515, China[5]Department of Radiology, the Third Affiliated Hospital of Sun Yat-sen University, No. 600, Tianhe Road, Tianhe District, Guangzhou 510630, China中山大学附属第三医院[6]Department of Pediatric Orthopedic, Center for Orthopedic Surgery, The Third Affiliated Hospital of Southern Medical University, No.183, Zhongshan Avenue West, Guangzhou 510515, China[7]School of Preclinical Medicine, Beijing University of Chinese Medicine, No.11, North Third Ring East Road, Chaoyang District, Beijing 100029, China[8]School of Chemical Engineering and Light Industry, Guangdong University of Technology, No.100, Waihuan West Road, Panyu District, Guangzhou 510006, China[9]Laboratory of Bone Tissue Engineering, Beijing Research Institute of Orthopaedics and Traumatology, Beijing JiShuiTan Hospital, No.31, Xinjiekou East Street, Xicheng District, Beijing 100035, China[10]Guangzhou Key Laboratory of Spine Disease Prevention and Treatment, Department of Spine Surgery, The Third Affiliated Hospital, Guangzhou Medical University, No. 63, Duobao Road, Liwan District, Guangzhou 510150, China
Electroconductive hydrogels are very attractive candidates for accelerated spinal cord injury (SCI) repair because they match the electrical and mechanical properties of neural tissue. However, electroconductive hydrogel implantation can potentially aggravate inflammation, and hinder its repair efficacy. Bone marrow stem cell-derived exosomes (BMSC-exosomes) have shown immunomodulatory and tissue regeneration effects, therefore, neural tissue-like electroconductive hydrogels loaded with BMSC-exosomes are developed for the synergistic treatment of SCI. These exosomes-loaded electroconductive hydrogels modulate microglial M2 polarization via the NF-kappa B pathway, and synergistically enhance neuronal and oligodendrocyte differentiation of neural stem cells (NSCs) while inhibiting astrocyte differentiation, and also increase axon outgrowth via the PTEN/PI3K/AKT/mTOR pathway. Furthermore, exosomes combined electroconductive hydrogels significantly decrease the number of CD68-positive microglia, enhance local NSCs recruitment, and promote neuronal and axonal regeneration, resulting in significant functional recovery at the early stage in an SCI mouse model. Hence, the findings of this study demonstrate that the combination of electroconductive hydrogels and BMSC-exosomes is a promising therapeutic strategy for SCI repair.
基金:
This work was supported by the National Key R&D Program of China (Nos.
2018YFC1105304 and 2018YFC1105301), the National Natural Science
Foundation of China (Nos. 51932002, 51903087, 51772105, 51772106, and
31771080), and the Natural Science Foundation of Guangdong Province
(No. 2020A1515011369).
第一作者机构:[1]School of Materials Science and Engineering and National Engineering, Research Center for Tissue Restoration and Reconstruction, South China University of Technology, No. 381, Wushan Road, Tianhe District, Guangzhou 510641, China
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通讯作者:
推荐引用方式(GB/T 7714):
Lei Fan,Can Liu,Xiuxing Chen,et al.Exosomes-Loaded Electroconductive Hydrogel Synergistically Promotes Tissue Repair after Spinal Cord Injury via Immunoregulation and Enhancement of Myelinated Axon Growth[J].ADVANCED SCIENCE.2022,9(13):doi:10.1002/advs.202105586.
APA:
Lei Fan,Can Liu,Xiuxing Chen,Lei Zheng,Yan Zou...&Chengyun Ning.(2022).Exosomes-Loaded Electroconductive Hydrogel Synergistically Promotes Tissue Repair after Spinal Cord Injury via Immunoregulation and Enhancement of Myelinated Axon Growth.ADVANCED SCIENCE,9,(13)
MLA:
Lei Fan,et al."Exosomes-Loaded Electroconductive Hydrogel Synergistically Promotes Tissue Repair after Spinal Cord Injury via Immunoregulation and Enhancement of Myelinated Axon Growth".ADVANCED SCIENCE 9..13(2022)