{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T03:15:49Z","timestamp":1783653349431,"version":"3.55.0"},"reference-count":20,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01 HL134696"],"award-info":[{"award-number":["U01 HL134696"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL169401"],"award-info":[{"award-number":["HL169401"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL178144"],"award-info":[{"award-number":["HL178144"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32 HL007150"],"award-info":[{"award-number":["T32 HL007150"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006458","name":"Children's Hospital of Philadelphia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006458","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Transfusion"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Blood bank identification of antibodies against high\u2010prevalence antigens remains a challenge due to the scarcity of antigen\u2010negative reagent red cells sourced from blood donors. The MAM antigen, encoded by\n                      <jats:italic>EMP3<\/jats:italic>\n                      , is one such antigen associated with red cell alloimmunization and hemolytic disease of the fetus and newborn.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Study Design and Methods<\/jats:title>\n                    <jats:p>\n                      We used CRISPR\u2010Cas9 gene editing to generate an\n                      <jats:italic>EMP3<\/jats:italic>\n                      knockout (EMP3KO) induced pluripotent stem cell (iPSC) line from a type O, Rh null parent line, enabling production of rare MAM\u2010negative red blood cells. Since a prior study suggested that loss of EMP3 may enhance erythroid proliferation, we hypothesized that EMP3KO could both yield a rare reagent cell and potentially improve erythroid expansion to support scalable production. Transcriptomic analysis allowed us to further investigate the effect of\n                      <jats:italic>EMP3<\/jats:italic>\n                      loss in late erythroblasts.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>EMP3KO cells differentiated efficiently into erythroid cells, showing &gt;95% CD235\/CD71 co\u2010expression and orthochromatic erythroblast morphology. Compared to unedited cells, no proliferative advantage was observed, contrasting with prior non\u2010isogenic cell models. Agglutination assays confirmed complete loss of MAM antigen and demonstrated the diagnostic utility for identifying MAM antibodies. Transcriptomic profiling of EMP3KO erythroblasts revealed expression of key erythroid genes, as well as regulators of proliferation and heme metabolism, was comparable to the parent line.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>This study demonstrates that iPSC technology combined with gene editing can generate rare antigen\u2010negative RBCs for immunohematology applications. Beyond MAM, this platform offers a strategy to create additional rare RBC phenotypes, advancing precision transfusion medicine and improving antibody identification against high\u2010prevalence antigens.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/trf.70243","type":"journal-article","created":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T05:43:31Z","timestamp":1777095811000},"page":"1257-1264","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Rare antigen\u2010negative red blood cells from pluripotent stem cells for precision transfusion medicine"],"prefix":"10.1111","volume":"66","author":[{"given":"Naomi","family":"Gunawardena","sequence":"first","affiliation":[{"name":"Division of Hematology, Department of Pediatrics Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"},{"name":"Division of Transfusion Medicine, Department of Pathology and Laboratory Medicine Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun Hyung","family":"An","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology Perelman School of Medicine  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3981-1791","authenticated-orcid":false,"given":"Randall W.","family":"Veliquette","sequence":"additional","affiliation":[{"name":"Immunohematology and Genomics Laboratory New York Blood Center Enterprises  Rye New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edmund","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Pediatrics Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sambit","family":"Dalui","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Pediatrics Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2081-9692","authenticated-orcid":false,"given":"Kaoru","family":"Takasaki","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Pediatrics Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"},{"name":"Perelman School of Medicine  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Wafula","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Health Informatics Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah L.","family":"French","sequence":"additional","affiliation":[{"name":"Perelman School of Medicine  Philadelphia Pennsylvania USA"},{"name":"Center for Cellular and Molecular Therapeutics Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"},{"name":"Division of Experimental Pathology, Department of Pathology and Laboratory Medicine Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Pavani","sequence":"additional","affiliation":[{"name":"Perelman School of Medicine  Philadelphia Pennsylvania USA"},{"name":"Center for Cellular and Molecular Therapeutics Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"},{"name":"Division of Experimental Pathology, Department of Pathology and Laboratory Medicine Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stella T.","family":"Chou","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Pediatrics Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"},{"name":"Division of Transfusion Medicine, Department of Pathology and Laboratory Medicine Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"},{"name":"Perelman School of Medicine  Philadelphia Pennsylvania 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