{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T02:42:11Z","timestamp":1792464131335,"version":"4.5.0"},"reference-count":76,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T00:00:00Z","timestamp":1770163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100018693","name":"HORIZON EUROPE Framework Programme","doi-asserted-by":"publisher","award":["101056712"],"award-info":[{"award-number":["101056712"]}],"id":[{"id":"10.13039\/100018693","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Immunogenicity of allogeneic human induced pluripotent stem cell (hiPSC)-derived transplants limits their applicability in regenerative medicine. Selecting human leukocyte antigen (HLA)-homozygous hiPSC lines could be a mitigation strategy and haplo-matching would profoundly expand the number of potential recipients. Here we show deep immune-phenotyping of hiPSC-derived cardiomyocytes (iPS-CM) differentiated from four independent iPSC lines in three centers under chemically defined conditions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Broad immunophenotyping with 354 antibodies revealed differential expression of 101 immune-related molecules between iPS-CM and the parental hiPSC lines. We selected 54 key immune markers for deep immune-phenotyping by spectral flow cytometry at the single-cell level. We found that HLA-homozygous iPSCMs exhibit an overall stable immune-phenotype across HLA-homozygous and heterozygous hiPSC lines indicating a robust differentiation process. HLA-homozygous iPS-CM displayed significantly reduced HLA-ABC levels compared to heterozygous counterparts with an otherwise conserved immune-phenotype. Upon interferon gamma challenge as a surrogate of immune stress responsiveness, iPS-CM significantly upregulated HLA-ABC, -E, -F, PD-L1, PD-L2 and the 'don't eat me' signal CD47. As a proof-of-concept we used this panel to benchmark iPS-CM differentiation across three production sites in this study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>The data indicate generally stable immune-phenotype of iPS-CM produced at three different sites and support feasibility of monitoring iPS-CM identity by spectral flow cytometry.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1736994","type":"journal-article","created":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T05:33:46Z","timestamp":1770183226000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Deep immune-phenotyping of HLA-homozygous iPS-cardiomyocytes by spectral flow 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Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Diecke","sequence":"additional","affiliation":[{"name":"Max-Delbrueck-Center for Molecular Medicine (MDC)","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torsten","family":"Tonn","sequence":"additional","affiliation":[{"name":"Institute for Transfusion Medicine and Immunohematology, Goethe University Hospital Medical School","place":["Frankfurt, Germany"]},{"name":"German Red Cross Blood Donor Service Baden-Wuerttemberg-Hessen","place":["Frankfurt, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boris","family":"Greber","sequence":"additional","affiliation":[{"name":"Catalent D\u00fcsseldorf GmbH","place":["D\u00fcsseldorf, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Zweigerdt","sequence":"additional","affiliation":[{"name":"Department of Cardiac, Thoracic, Transplantation 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