Evidence map›Paper›PMID 42032930›Full record

ArticleTransfusion2026

Rare antigen-negative red blood cells from pluripotent stem cells for precision transfusion medicine.

Naomi Gunawardena, Hyun Hyung An, Randall W Veliquette, Edmund Carvalho, Sambit Dalui, Kaoru Takasaki, Eric Wafula, Deborah L French, Giulia Pavani, Stella T Chou

Abstract read
In one paragraph

Article in Transfusion, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Naomi GunawardenaDivision of Hematology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Hyun Hyung AnDepartment of Cell and Molecular Biology, Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
Randall W VeliquetteImmunohematology and Genomics Laboratory, New York Blood Center Enterprises, Rye, New York, USA.ORCID https://orcid.org/0009-0003-3981-1791
Edmund CarvalhoDivision of Hematology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Sambit DaluiDivision of Hematology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Kaoru TakasakiDivision of Hematology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.ORCID https://orcid.org/0000-0002-2081-9692
Eric WafulaDepartment of Biomedical and Health Informatics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Deborah L FrenchPerelman School of Medicine, Philadelphia, Pennsylvania, USA.
Giulia PavaniPerelman School of Medicine, Philadelphia, Pennsylvania, USA.
Stella T ChouDivision of Hematology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

Funding

Improving transfusion therapy for patients with sickle cell disease with pluripotent stem cell-derived red cellsU01HL134696 · NHLBI · CHILDREN'S HOSP OF PHILADELPHIA · PI CHOU, STELLA T · 2016 to 2022
$8.3M
RED CELL HEMOGLOBIN RESEARCH TRAINING PROGRAMT32HL007150 · NHLBI · CHILDREN'S HOSP OF PHILADELPHIA · PI STELLA T CHOU, Mortimer Poncz · 1985 to 2026
$7.4M
A precision therapy approach to red cell transfusion for sickle cell diseaseR01HL169401 · NHLBI · CHILDREN'S HOSP OF PHILADELPHIA · PI STELLA T CHOU · 2024 to 2026
$2.4M
Manufacturing Process Intensification for Pluripotent Stem Cell-Derived Rare Red Cell ProductionR41HL178144 · NHLBI · SAFI BIOTHERAPEUTICS INC · PI CHOU, STELLA T, THOMAS, ROBERT JAMES · 2025 to 2025
$568k
Children's Hospital of Philadelphia Breakthrough FundsDistinguished Chair in PediatricsMizuno FundsNHLBI NIH HHS R01 HL169401NHLBI NIH HHS R41 HL178144NHLBI NIH HHS T32 HL007150NHLBI NIH HHS U01 HL134696NIH HHS HL169401NIH HHS HL178144NIH HHS T32 HL007150NIH HHS U01 HL134696
6 · The paper itself

Abstract

backgroundBlood bank identification of antibodies against high-prevalence antigens remains a challenge due to the scarcity of antigen-negative reagent red cells sourced from blood donors. The MAM antigen, encoded by EMP3, is one such antigen associated with red cell alloimmunization and hemolytic disease of the fetus and newborn. STUDY DESIGN AND

methodsWe used CRISPR-Cas9 gene editing to generate an EMP3 knockout (EMP3KO) induced pluripotent stem cell (iPSC) line from a type O, Rh null parent line, enabling production of rare MAM-negative 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 EMP3 loss in late erythroblasts.

resultsEMP3KO cells differentiated efficiently into erythroid cells, showing >95% CD235/CD71 co-expression and orthochromatic erythroblast morphology. Compared to unedited cells, no proliferative advantage was observed, contrasting with prior non-isogenic 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. DISCUSSION: This study demonstrates that iPSC technology combined with gene editing can generate rare antigen-negative 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-prevalence antigens.

Indexed as

ErythrocytesInduced Pluripotent Stem CellsPluripotent Stem CellsTransfusion MedicineErythroblastsHumansalloimmunizationinduced pluripotent stem cellsMAM antigenrare red blood cells

Identifiers

PMID42032930
PMCPMC13350276

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.