{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T15:06:13Z","timestamp":1789571173921,"version":"build-2803163510"},"reference-count":26,"publisher":"BMJ","issue":"9","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"unspecified","delay-in-days":15,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Guidon Pharmaceutics","award":["NA"],"award-info":[{"award-number":["NA"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2026,8,26]]},"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Cell-based therapies represent a promising therapeutic strategy for enhancing neurological recovery after stroke. Preclinical studies have demonstrated the efficacy of stem cell-derived exosomes in animal models of ischaemic stroke. We aim to evaluate the safety and preliminary efficacy of allogeneic human induced pluripotent stem cell (iPSC)-derived exosomes in patients with acute ischaemic stroke.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>This is a multicentre, prospective, phase I\/II clinical trial conducted in China between October 2023 and June 2026. Eligible participants will be patients with a diagnosis of cortical ischaemic stroke, a baseline National Institutes of Health Stroke Scale (NIHSS) score of 6\u201320 and enrolment within 1\u20137\u2009days after symptom onset. Stage 1 is a dose-escalation study including three different dose levels (n=3 per dose). Stage 2 is an expanded safety and preliminary efficacy phase with a randomised, double-blind, placebo-controlled design. In Stage 2, 20 patients will be randomised 1:1 to receive the highest safe dose identified in Stage 1 or placebo. The primary endpoint is the incidence of serious adverse events within 90 days. Secondary efficacy endpoints include the proportion of patients achieving a modified Rankin Scale (mRS) score of 0\u20132 at 90 days, ordinal mRS distribution at 90 days and changes in NIHSS and Barthel Index scores at 90 days, as well as EuroQol-5D-5L and Montreal Cognitive Assessment (MoCA) scores at 90 days.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>This protocol was written according to the general ethical guidelines of the Declaration of Helsinki and approved by the Ethics Committee of Xuanwu Hospital Capital Medical University (approval number [2023]161), the Third People\u2019s Hospital of Liaocheng, the First People\u2019s Hospital of Chenzhou, Zibo Municipal Hospital and Mianyang Central Hospital. Results of this study will be disseminated through peer-reviewed publication.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT06138210\">NCT06138210<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2025-115350","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T14:55:20Z","timestamp":1789570520000},"page":"e115350","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical safety and preliminary efficacy of allogeneic human induced pluripotent stem cell-derived exosomes in patients with acute ischaemic stroke: protocol of a phase I\/II clinical trial in China"],"prefix":"10.1136","volume":"16","clinical-trial-number":[{"clinical-trial-number":"nct06138210","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct06138210","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9374-7589","authenticated-orcid":false,"given":"Gaoting","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Neurology, Xuanwu Hospital Capital Medical University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8113-8276","authenticated-orcid":false,"given":"Yingting","family":"Zuo","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xuanwu Hospital Capital Medical University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Li","sequence":"additional","affiliation":[{"name":"CAMS Key Laboratory for T Cell and Immunotherapy, State Key Laboratory of Medical Molecular Biology, Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing, China"},{"name":"Guidon Pharmaceutics, Ltd, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenwen","family":"Bian","sequence":"additional","affiliation":[{"name":"Department of Neurology, Zibo Municipal Hospital, Zibo, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingli","family":"Mu","sequence":"additional","affiliation":[{"name":"Department of Traditional Chinese Medicine, The Third People Hospital in Liaocheng, Liaocheng, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxi","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Neurology, The First People\u2019s Hospital of Chenzhou, Chenzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ganghua","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Neurology, The First People\u2019s Hospital of Chenzhou, Chenzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ran","family":"Mo","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xuanwu Hospital Capital Medical University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shujuan","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xuanwu Hospital Capital Medical University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xuanwu Hospital Capital Medical University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieying","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xuanwu Hospital Capital Medical University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Chen","sequence":"additional","affiliation":[{"name":"Guidon Pharmaceutics, Ltd, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0114-6402","authenticated-orcid":false,"given":"Qingfeng","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xuanwu Hospital Capital Medical University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daiquan","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xuanwu Hospital Capital Medical University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianmei","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xuanwu Hospital Capital Medical University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianmin","family":"Zhang","sequence":"additional","affiliation":[{"name":"CAMS Key Laboratory for T Cell and Immunotherapy, State Key Laboratory of Medical Molecular Biology, Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing, China"},{"name":"Guidon Pharmaceutics, Ltd, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3075-5434","authenticated-orcid":false,"given":"Junwei","family":"Hao","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xuanwu Hospital Capital Medical University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"key":"2026091607551006000_16.9.e115350.1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(18)30499-X"},{"key":"2026091607551006000_16.9.e115350.2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.111.618850"},{"key":"2026091607551006000_16.9.e115350.3","doi-asserted-by":"publisher","DOI":"10.1161\/STR.0000000000000211"},{"key":"2026091607551006000_16.9.e115350.4","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(16)00163-x"},{"key":"2026091607551006000_16.9.e115350.5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1365-2184.2010.00718.x","article-title":"Cell therapy for ischaemic stroke","volume":"44 Suppl 1","author":"Hess","year":"2011","journal-title":"Cell Prolif"},{"key":"2026091607551006000_16.9.e115350.6","doi-asserted-by":"publisher","DOI":"10.5966\/sctm.2011-0039"},{"key":"2026091607551006000_16.9.e115350.7","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(02)00040-6"},{"key":"2026091607551006000_16.9.e115350.8","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1517\/14712598.2015.1040386","article-title":"Adipose tissue-derived mesenchymal stem cells as a strategy to improve recovery after stroke","volume":"15","author":"Guti\u00e9rrez-Fern\u00e1ndez","year":"2015","journal-title":"Expert Opin Biol Ther"},{"key":"2026091607551006000_16.9.e115350.9","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2021-051790","article-title":"Allogeneic adipose tissue-derived mesenchymal stem cells in ischaemic stroke (AMASCIS-02): a phase IIb, multicentre, double-blind, placebo-controlled clinical trial protocol","volume":"11","author":"de Celis-Ruiz","year":"2021","journal-title":"BMJ Open"},{"key":"2026091607551006000_16.9.e115350.10","doi-asserted-by":"crossref","first-page":"9636897221083863","DOI":"10.1177\/09636897221083863","article-title":"Final Results of Allogeneic Adipose Tissue-Derived Mesenchymal Stem Cells in Acute Ischemic Stroke (AMASCIS): A Phase II, Randomized, Double-Blind, Placebo-Controlled, Single-Center, Pilot Clinical Trial","volume":"31","author":"de Celis-Ruiz","year":"2022","journal-title":"Cell Transplant"},{"key":"2026091607551006000_16.9.e115350.11","doi-asserted-by":"publisher","DOI":"10.1038\/nature06534"},{"key":"2026091607551006000_16.9.e115350.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2009.07.001"},{"key":"2026091607551006000_16.9.e115350.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcyt.2018.06.012"},{"key":"2026091607551006000_16.9.e115350.14","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-018-0126-4"},{"key":"2026091607551006000_16.9.e115350.15","doi-asserted-by":"crossref","DOI":"10.3390\/biom12010115","article-title":"Potential Role of Exosomes in Ischemic Stroke Treatment","volume":"12","author":"Jiang","year":"2022","journal-title":"Biomolecules"},{"key":"2026091607551006000_16.9.e115350.16","doi-asserted-by":"publisher","DOI":"10.2174\/1381612823666170913164738"},{"key":"2026091607551006000_16.9.e115350.17","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.117.018292"},{"key":"2026091607551006000_16.9.e115350.18","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-018-0654-7"},{"key":"2026091607551006000_16.9.e115350.19","doi-asserted-by":"crossref","DOI":"10.3390\/cells11050820","article-title":"Therapeutic Potential of a Combination of Electroacupuncture and Human iPSC-Derived Small Extracellular Vesicles for Ischemic Stroke","volume":"11","author":"Deng","year":"2022","journal-title":"Cells"},{"key":"2026091607551006000_16.9.e115350.20","doi-asserted-by":"publisher","DOI":"10.7150\/thno.30879"},{"key":"2026091607551006000_16.9.e115350.21","article-title":"Correction to: MicroRNA-17\u201392 Cluster in Exosomes Enhance Neuroplasticity and Functional Recovery After Stroke in Rats","volume":"48","year":"2017","journal-title":"Stroke"},{"key":"2026091607551006000_16.9.e115350.22","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1186\/s13287-020-01601-1","article-title":"Low dose of extracellular vesicles identified that promote recovery after ischemic stroke","volume":"11","author":"Otero-Ortega","year":"2020","journal-title":"Stem Cell Res Ther"},{"key":"2026091607551006000_16.9.e115350.23","doi-asserted-by":"publisher","DOI":"10.5966\/sctm.2015-0078"},{"key":"2026091607551006000_16.9.e115350.24","doi-asserted-by":"publisher","DOI":"10.4103\/0976-0105.177703"},{"key":"2026091607551006000_16.9.e115350.25","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2006.01.015"},{"key":"2026091607551006000_16.9.e115350.26","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.117.018223"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2025-115350","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T14:55:22Z","timestamp":1789570522000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2025-115350"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":26,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9,16]]},"published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1136\/bmjopen-2025-115350"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2025-115350","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9]]}}}