{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T16:00:41Z","timestamp":1786118441089,"version":"build-2736575974"},"reference-count":24,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"vor","delay-in-days":17,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Megakaryon Corporation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Platelet products are essential for preventing and treating bleeding in patients with thrombocytopenia. However, their short shelf life and reliance on voluntary blood donations pose significant challenges to maintaining a stable supply. To overcome these limitations, induced pluripotent stem cell-derived platelets (iPSC-PLTs) have emerged as a promising alternative. The clinical application of iPSC-PLTs succeeded in demonstrating safety in an autologous transfusion setting; however, allogeneic applications remain unexplored. Here, we report the world\u2019s first clinical evaluation of an allogeneic iPSC-PLT product. An immortalized megakaryocyte cell line (imMKCL) was established from an iPSC line by introducing 3 inducible genes\u2014c-MYC, BMI1, and BCL-XL\u2014and subsequently generating master and working cell banks. Using the working cell bank and turbulent flow bioreactors, an allogeneic iPSC-PLT product, MEG-002, was successfully produced with clinically relevant quality and yield. MEG-002 underwent comprehensive structural and functional characterization, including in vivo efficacy testing in rabbit models, which confirmed its functionality. Preclinical safety studies revealed no concerns. A clinical trial was conducted in accordance with ethical and regulatory standards in Japan. MEG-002 was infused into a patient with aplastic anemia at a dose of 6\u2009\u00d7\u20091010 platelets. No adverse events were reported, and no clinically significant changes were observed in any assessments. Furthermore, a transient increase in platelet count and evidence of iPSC-PLT circulation were observed. Despite being descriptive observations from a single subject, these findings suggest the safety and potential efficacy of allogeneic iPSC-PLTs in humans. The clinical trial is registered with the Japan Registry of Clinical Trials (jRCT2053210068).<\/jats:p>","DOI":"10.1093\/stcltm\/szag067","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T16:22:58Z","timestamp":1782922978000},"source":"Crossref","is-referenced-by-count":0,"title":["First evidence of the circulation of induced pluripotent stem cell-derived platelets in humans"],"prefix":"10.1093","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-8102-7238","authenticated-orcid":false,"given":"Kazumasa","family":"Takao","sequence":"first","affiliation":[{"name":"Megakaryon Corporation , Kyoto 600-8813,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Kumagae","sequence":"additional","affiliation":[{"name":"Megakaryon Corporation , Kyoto 600-8813,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6704-3633","authenticated-orcid":false,"given":"Junya","family":"Kanda","sequence":"additional","affiliation":[{"name":"Department of Hematology, Kyoto University Hospital , Kyoto 606-8507,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidenori","family":"Hirose","sequence":"additional","affiliation":[{"name":"Megakaryon Corporation , Kyoto 600-8813,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromichi","family":"Konno","sequence":"additional","affiliation":[{"name":"Megakaryon Corporation , Kyoto 600-8813,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoyuki","family":"Inoue","sequence":"additional","affiliation":[{"name":"Megakaryon Corporation , Kyoto 600-8813,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4008-8938","authenticated-orcid":false,"given":"Yuya","family":"Sato","sequence":"additional","affiliation":[{"name":"Megakaryon Corporation , Kyoto 600-8813,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuko","family":"Hazama","sequence":"additional","affiliation":[{"name":"Megakaryon Corporation , Kyoto 600-8813,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaichi","family":"Hasegawa","sequence":"additional","affiliation":[{"name":"Megakaryon Corporation , Kyoto 600-8813,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0319-8537","authenticated-orcid":false,"given":"Asano","family":"Asami","sequence":"additional","affiliation":[{"name":"Megakaryon Corporation , Kyoto 600-8813,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuhiro","family":"Nishimura","sequence":"additional","affiliation":[{"name":"Megakaryon Corporation , Kyoto 600-8813,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2234-769X","authenticated-orcid":false,"given":"Akira","family":"Sawaguchi","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Faculty of Medicine, University of Miyazaki , Miyazaki 889-1692,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7678-4284","authenticated-orcid":false,"given":"Akifumi","family":"Takaori-Kondo","sequence":"additional","affiliation":[{"name":"Department of Hematology, Kyoto University Hospital , Kyoto 606-8507,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4498-8836","authenticated-orcid":false,"given":"Kenichi","family":"Akamatsu","sequence":"additional","affiliation":[{"name":"Megakaryon Corporation , Kyoto 600-8813,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,8,6]]},"reference":[{"key":"2026080612025470400_szag067-B1","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1001\/jama.2025.7529","article-title":"Platelet transfusion: 2025 AABB and ICTMG international clinical practice guidelines","volume":"334","author":"Metcalf","year":"2025","journal-title":"JAMA"},{"key":"2026080612025470400_szag067-B2","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1186\/s13054-018-2114-x","article-title":"Platelet storage duration and its clinical and transfusion outcomes: a systematic 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Haematol"},{"key":"2026080612025470400_szag067-B6","doi-asserted-by":"crossref","first-page":"3319","DOI":"10.1182\/blood-2012-09-455428","article-title":"Challenges and promises for the development of donor-independent platelet transfusions","volume":"121","author":"Lambert","year":"2013","journal-title":"Blood"},{"key":"2026080612025470400_szag067-B7","doi-asserted-by":"crossref","first-page":"985","DOI":"10.3390\/life15060985","article-title":"Platelet transfusions: current practices and emerging alternatives in the United States","volume":"15","author":"Friedman","year":"2025","journal-title":"Life"},{"key":"2026080612025470400_szag067-B8","doi-asserted-by":"crossref","first-page":"2398","DOI":"10.1182\/blood.2022017296","article-title":"iPLAT1: the first-in-human clinical trial of iPSC-derived platelets as a phase 1 autologous transfusion 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