详情页 - 广东省中医院知识库

当前位置：首页 > 详情页

Spinal cord injury target-immunotherapy with TNF-α autoregulated and feedback-controlled human umbilical cord mesenchymal stem cell derived exosomes remodelled by CRISPR/Cas9 plasmid.

文献详情

资源类型：

Pubmed体系：

收录情况： ◇ EI

作者：

机构： [1]The Fifth Affiliated Hospital (Heyuan Shenhe People's Hospital), Jinan University, Heyuan 517000, China [2]Department of Orthopedics, The First Affiliated Hospital, Jinan University, Guangzhou 510632, China [3]Tsinghua-Berkeley Shenzhen Institute, Tsinghua University, Shenzhen 518055, China [4]School of Chinese Medicine, Jinan University, Guangzhou, Guangdong Province 510632, China [5]Department of Orthopedics, The Affiliated Zhuzhou Hospital Xiangya Medical College CSU, Zhuzhou 412007, China [6]Guangdong-Hongkong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory, Jinan University, Guangzhou 510632, China [7]Zhuhai Precision Medical Center, Zhuhai People's Hospital (Zhuhai Hospital Affiliated with Jinan University), Jinan University, Zhuhai 519000, Guangdong, China [8]The Biomedical Translational Research Institute, Jinan University Faculty of Medical Science, Jinan University, Guangzhou 510632, China [9]Intensive Care Unit, The First Affiliated Hospital, Jinan University, Guangzhou 510632, China [10]The Affiliated Hospital (Jiangmen Traditional Chinese Medicine Hospital), Jinan University, Guangzhou 510632, China

出处：

DOI：

ISSN：

关键词： CRISPR/Cas9 Exosomes CAQK peptide TNF-α Spinal cord injury

摘要：

Human umbilical cord mesenchymal stem cell (hucMSC) derived exosomes (EXOs) have been investigated as a new treatment for spinal cord injury (SCI) because of their anti-inflammatory, anti-apoptotic, angiogenesis-promoting, and axonal regeneration properties. The CAQK peptide found in the brains of mice and humans after trauma has recently been found to specifically bind to the injured site after SCI. Thus, we developed a nanocarrier system called EXO-C@P based on hucMSC exosomes remodelled by the CRISPR/Cas9 plasmid to control inflammation and modified by the CAQK peptide. EXO-C@P was shown to effectively accumulate at the injury site and saturate the macrophages to significantly reduce the expression of inflammatory cytokines in a mouse model of SCI. Moreover, EXO-C@P treatment improved the performance of mice in behavioural assessments and upregulated soluble tumour necrosis factor receptor-1 (sTNFR1) in serum and at the trauma site after SCI surgery, but lowered the proportion of iNOS+ cells and the concentration of proinflammatory factors. In conclusion, EXO-C@P provides an effective alternative to multiple topical administration and drug delivery approaches for the treatment of SCI. STATEMENT OF SIGNIFICANCE: SCI is a serious disease characterised by a high incidence, high disability rate, and high medical costs, and has become a global medical problem. Several studies have shown that the inflammatory response is the critical inducer of secondary injury after SCI. The inflammatory cytokine TNF-α is considered to be one of the most significant therapeutic targets for autoimmune diseases. Antibodies targeting TNF-α and sTNFR1 are capable of neutralising free TNF-α. In this study, exosomes in the CRISPR/Cas9 system were used to establish stem cells with an autoregulated and feedback-controlled TNF-α response, with these cells secreting sTNFR1, which neutralised TNF-α and antagonised the inflammation stimulated by TNF-α. Moreover, the plasmid was combined with CAQK, which targeted the injury site and promoted the recovery of SCI function.Copyright © 2021 Elsevier B.V. All rights reserved.

基金：

语种：

PubmedID：

中科院(CAS)分区：

出版当年[2020]版：

大类 | 2 区工程技术

小类 | 2 区材料科学：生物材料

最新[2025]版：

无

第一作者：

第一作者机构： [1]The Fifth Affiliated Hospital (Heyuan Shenhe People's Hospital), Jinan University, Heyuan 517000, China [2]Department of Orthopedics, The First Affiliated Hospital, Jinan University, Guangzhou 510632, China [3]Tsinghua-Berkeley Shenzhen Institute, Tsinghua University, Shenzhen 518055, China

共同第一作者：

通讯作者：

通讯机构： [1]The Fifth Affiliated Hospital (Heyuan Shenhe People's Hospital), Jinan University, Heyuan 517000, China [2]Department of Orthopedics, The First Affiliated Hospital, Jinan University, Guangzhou 510632, China [6]Guangdong-Hongkong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory, Jinan University, Guangzhou 510632, China [8]The Biomedical Translational Research Institute, Jinan University Faculty of Medical Science, Jinan University, Guangzhou 510632, China [*1]The Biomedical Translational Research Institute, Jinan University Faculty of Medical Science, Jinan University, Guangzhou 510632, China [*2]The Fifth Affiliated Hospital (Heyuan Shenhe People's Hospital), Jinan University, Heyuan 517000, China

推荐引用方式(GB/T 7714)：

APA：

MLA：

Spinal cord injury target-immunotherapy with TNF-α autoregulated and feedback-controlled human umbilical cord mesenchymal stem cell derived exosomes remodelled by CRISPR/Cas9 plasmid.

文献详情

相关文献