{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T15:25:15Z","timestamp":1790090715939,"version":"4.0.1"},"reference-count":30,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T00:00:00Z","timestamp":1758499200000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100017596","name":"Natural Science Basic Research Program of Shaanxi Province","doi-asserted-by":"publisher","award":["2023\u2010JC\u2010ZD\u201052"],"award-info":[{"award-number":["2023\u2010JC\u2010ZD\u201052"]}],"id":[{"id":"10.13039\/501100017596","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To investigate whether genetically modifying human umbilical cord\u2010derived mesenchymal stem cells (MSC) to overexpress the CXCR4 receptor can enhance their therapeutic efficacy for treating brain injury following cardiac arrest (CA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>MSC were engineered to overexpress CXCR4 (CXCR4\u2010MSC) via lentiviral transduction. The migration capacity of these cells was tested using in\u00a0vitro chemotaxis assays. In a rat model of CA\/CPR, the homing ability of CXCR4\u2010MSC to the brain was tracked in\u00a0vivo, 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Result<\/jats:title>\n                    <jats:p>CXCR4 overexpression significantly enhanced the migration of MSC in\u00a0vitro and their homing to injured brain tissue in\u00a0vivo. Treatment with CXCR4\u2010MSC markedly reduced neuronal death and improved neurological recovery in resuscitated rats. This was accompanied by decreased expression of NLRP3. Furthermore, exosomes derived from CXCR4\u2010MSC were found to suppress pyroptosis\u2010related proteins (NLRP3\/ASC\/GSDMD) in post\u2010CPR neurons, an effect that was reversed upon exosome inhibition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Genetic modification to overexpress CXCR4 enhances the therapeutic efficacy of MSC for CA\u2010induced brain injury by promoting their migration to the brain via the CXCL12\/CXCR4 axis. A key mechanism of this protection is exosome\u2010mediated inhibition of neuronal pyroptosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cns.70621","type":"journal-article","created":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T05:18:17Z","timestamp":1758604697000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Genetic Modification of Mesenchymal Stem Cell to Overexpress\n                    <scp>CXCR4<\/scp>\n                    Enhances Treatment Efficacy for Brain Injury After Cardiopulmonary Resuscitation"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7134-0825","authenticated-orcid":false,"given":"Yongfei","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Anesthesiology Tangdu Hospital, the Fourth Military Medical University  Xi'an Shaanxi 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