{"title":"基因修饰间充质干细胞过表达CXCR4提高心肺复苏后脑损伤的治疗效果","authors":"Yongfei Liu, Li Zhang, Jingxiang Wang, Yuan Qin, Liang Zhang, Anlin Yue, Zhongting Wang, Xiao Xiao, Shuang Wang, Lu Huang, Changjun Gao","doi":"10.1111/cns.70621","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Aim</h3>\n \n <p>To investigate whether genetically modifying human umbilical cord-derived mesenchymal stem cells (MSC) to overexpress the CXCR4 receptor can enhance their therapeutic efficacy for treating brain injury following cardiac arrest (CA).</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>MSC were engineered to overexpress CXCR4 (CXCR4-MSC) via lentiviral transduction. The migration capacity of these cells was tested using in vitro chemotaxis assays. In a rat model of CA/CPR, the homing ability of CXCR4-MSC to the brain was tracked in vivo, and their therapeutic effects on neuronal death and neurological recovery were assessed. The role of exosomes and their impact on key proteins (NLRP3, ASC, GSDMD) in the pyroptosis pathway was also investigated.</p>\n </section>\n \n <section>\n \n <h3> Result</h3>\n \n <p>CXCR4 overexpression significantly enhanced the migration of MSC in vitro and their homing to injured brain tissue in vivo. Treatment with CXCR4-MSC markedly reduced neuronal death and improved neurological recovery in resuscitated rats. This was accompanied by decreased expression of NLRP3. Furthermore, exosomes derived from CXCR4-MSC were found to suppress pyroptosis-related proteins (NLRP3/ASC/GSDMD) in post-CPR neurons, an effect that was reversed upon exosome inhibition.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>Genetic modification to overexpress CXCR4 enhances the therapeutic efficacy of MSC for CA-induced brain injury by promoting their migration to the brain via the CXCL12/CXCR4 axis. A key mechanism of this protection is exosome-mediated inhibition of neuronal pyroptosis.</p>\n </section>\n </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 9","pages":""},"PeriodicalIF":5.0000,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70621","citationCount":"0","resultStr":"{\"title\":\"Genetic Modification of Mesenchymal Stem Cell to Overexpress CXCR4 Enhances Treatment Efficacy for Brain Injury After Cardiopulmonary Resuscitation\",\"authors\":\"Yongfei Liu, Li Zhang, Jingxiang Wang, Yuan Qin, Liang Zhang, Anlin Yue, Zhongting Wang, Xiao Xiao, Shuang Wang, Lu Huang, Changjun Gao\",\"doi\":\"10.1111/cns.70621\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Aim</h3>\\n \\n <p>To investigate whether genetically modifying human umbilical cord-derived mesenchymal stem cells (MSC) to overexpress the CXCR4 receptor can enhance their therapeutic efficacy for treating brain injury following cardiac arrest (CA).</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>MSC were engineered to overexpress CXCR4 (CXCR4-MSC) via lentiviral transduction. The migration capacity of these cells was tested using in vitro chemotaxis assays. In a rat model of CA/CPR, the homing ability of CXCR4-MSC to the brain was tracked in vivo, and their therapeutic effects on neuronal death and neurological recovery were assessed. The role of exosomes and their impact on key proteins (NLRP3, ASC, GSDMD) in the pyroptosis pathway was also investigated.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Result</h3>\\n \\n <p>CXCR4 overexpression significantly enhanced the migration of MSC in vitro and their homing to injured brain tissue in vivo. Treatment with CXCR4-MSC markedly reduced neuronal death and improved neurological recovery in resuscitated rats. This was accompanied by decreased expression of NLRP3. Furthermore, exosomes derived from CXCR4-MSC were found to suppress pyroptosis-related proteins (NLRP3/ASC/GSDMD) in post-CPR neurons, an effect that was reversed upon exosome inhibition.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusion</h3>\\n \\n <p>Genetic modification to overexpress CXCR4 enhances the therapeutic efficacy of MSC for CA-induced brain injury by promoting their migration to the brain via the CXCL12/CXCR4 axis. A key mechanism of this protection is exosome-mediated inhibition of neuronal pyroptosis.</p>\\n </section>\\n </div>\",\"PeriodicalId\":154,\"journal\":{\"name\":\"CNS Neuroscience & Therapeutics\",\"volume\":\"31 9\",\"pages\":\"\"},\"PeriodicalIF\":5.0000,\"publicationDate\":\"2025-09-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70621\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"CNS Neuroscience & Therapeutics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/cns.70621\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"CNS Neuroscience & Therapeutics","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/cns.70621","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
Genetic Modification of Mesenchymal Stem Cell to Overexpress CXCR4 Enhances Treatment Efficacy for Brain Injury After Cardiopulmonary Resuscitation
Aim
To investigate whether genetically modifying human umbilical cord-derived mesenchymal stem cells (MSC) to overexpress the CXCR4 receptor can enhance their therapeutic efficacy for treating brain injury following cardiac arrest (CA).
Methods
MSC were engineered to overexpress CXCR4 (CXCR4-MSC) via lentiviral transduction. The migration capacity of these cells was tested using in vitro chemotaxis assays. In a rat model of CA/CPR, the homing ability of CXCR4-MSC to the brain was tracked in vivo, and their therapeutic effects on neuronal death and neurological recovery were assessed. The role of exosomes and their impact on key proteins (NLRP3, ASC, GSDMD) in the pyroptosis pathway was also investigated.
Result
CXCR4 overexpression significantly enhanced the migration of MSC in vitro and their homing to injured brain tissue in vivo. Treatment with CXCR4-MSC markedly reduced neuronal death and improved neurological recovery in resuscitated rats. This was accompanied by decreased expression of NLRP3. Furthermore, exosomes derived from CXCR4-MSC were found to suppress pyroptosis-related proteins (NLRP3/ASC/GSDMD) in post-CPR neurons, an effect that was reversed upon exosome inhibition.
Conclusion
Genetic modification to overexpress CXCR4 enhances the therapeutic efficacy of MSC for CA-induced brain injury by promoting their migration to the brain via the CXCL12/CXCR4 axis. A key mechanism of this protection is exosome-mediated inhibition of neuronal pyroptosis.
期刊介绍：
CNS Neuroscience & Therapeutics provides a medium for rapid publication of original clinical, experimental, and translational research papers, timely reviews and reports of novel findings of therapeutic relevance to the central nervous system, as well as papers related to clinical pharmacology, drug development and novel methodologies for drug evaluation. The journal focuses on neurological and psychiatric diseases such as stroke, Parkinson’s disease, Alzheimer’s disease, depression, schizophrenia, epilepsy, and drug abuse.
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