{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T06:45:16Z","timestamp":1782715516698,"version":"3.54.5"},"reference-count":49,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T00:00:00Z","timestamp":1782432000000},"content-version":"vor","delay-in-days":25,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82372204"],"award-info":[{"award-number":["82372204"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82472234"],"award-info":[{"award-number":["82472234"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Cardiac arrest (CA) is a leading cause of death globally. Exosomes derived from mesenchymal stem cells exhibit favourable production, storage, and safety characteristics, making them a promising alternative for post\u2010CA resuscitation. We assessed the safety, biodistribution, and protective effects of human embryonic stem cell\u2010derived immunity\u2010and\u2010matrix regulatory cells (hESC\u2010IMRC\u2010Exo) for post\u2010CA resuscitation cardiac\/cerebral injuries, and preliminarily explored its underlying molecular mechanism. The biotoxicity of IMRC\u2010Exo was evaluated in AC16 and HT22 cells and in mice; its biodistribution was traced using fluorescently labelled IMRC\u2010Exo. Protective effects were examined in H\/R\u2010treated cells and rat and swine CA models. We found that IMRC\u2010Exo did not induce apoptosis or oxidative stress in AC16 or HT22 cells. IMRC\u2010Exo was also safe in mice, with normal body weight, blood indices, and histopathology. Pharmacokinetic analysis revealed rapid multi\u2010organ distribution, peaking at 24\u2009h with a 7\u2010day half\u2010life. For efficacy study, IMRC\u2010Exo reduced LDH release, ROS levels, and apoptosis in H\/R\u2010treated cells. In rat, IMRC\u2010Exo dose\u2010dependently (0.5\u00d7, 1\u00d7, 2\u00d7) reduced serum biomarkers, improved neurological function, and attenuated inflammation. In swine, single\u2010dose IMRC\u2010Exo (1\u00d7) reduced injury biomarkers, improved neurological function, and attenuated inflammation. Furthermore, in a separate rat group, IMRC\u2010Exo improved 7\u2010day survival and neurological function. Mechanistically, the protective effects of IMRC\u2010Exo were mediated by its secreted miR\u201021\u20105p, which attenuated H\/R\u2010induced apoptosis and inflammation by targeting PDCD4. This study demonstrated IMRC\u2010Exo, a safe and effective therapeutic, distributed rapidly via the bloodstream to target organs and protected against post\u2010resuscitation cardiac\/cerebral injuries, potentially through the miR\u201021\u20105p\/PDCD4 axis.<\/jats:p>","DOI":"10.1111\/jcmm.71264","type":"journal-article","created":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T04:12:19Z","timestamp":1782533539000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Assessment of\n                    <scp>hESC<\/scp>\n                    \u2010\n                    <scp>IMRC<\/scp>\n                    \u2010Exo for Cardiac and Cerebral Injuries Post\u2010Cardiac Arrest Resuscitation: Safety, Pharmacokinetics, and Efficacy"],"prefix":"10.1111","volume":"30","author":[{"given":"Huijuan","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Emergency Medicine, Second Affiliated Hospital Zhejiang 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Burn, and Medical Rescue  Hangzhou China"},{"name":"Zhejiang Province Clinical Research Center for Emergency and Critical Care Medicine  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Biotechnology, Xianghu Laboratory  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Wang","sequence":"additional","affiliation":[{"name":"Oujiang Laboratory  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziwei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Second Affiliated Hospital Zhejiang University School of Medicine  Hangzhou China"},{"name":"Zhejiang Key Laboratory of Trauma, Burn, and Medical Rescue  Hangzhou China"},{"name":"Zhejiang Province Clinical Research Center for Emergency and Critical Care Medicine  Hangzhou 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