Evidence map›Paper›PMID 40628261›Full record

ArticleCell reports. Medicine2025

Immunogenicity of autologous and allogeneic human primary cholangiocyte organoid cellular therapies.

Sandra Petrus-Reurer, Winnie Lei, Olivia Tysoe, Maelle Mairesse, Adrian Baez-Ortega, Julia Jones, Thomas Tan, Sylvia Rehakova, Krishnaa T Mahbubani, Cara Brodie and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports. Medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. Article
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

15 authors.

Sandra Petrus-ReurerDepartment of Surgery, University of Cambridge and NIHR Cambridge Biomedical Research Centre, Cambridge CB2 0QQ, UK. Electronic address: sp2016@cam.ac.uk.
Winnie LeiDepartment of Surgery, University of Cambridge and NIHR Cambridge Biomedical Research Centre, Cambridge CB2 0QQ, UK; Milner Therapeutics Institute, University of Cambridge, Cambridge CB2 0AW, UK.
Olivia TysoeDepartment of Surgery, University of Cambridge and NIHR Cambridge Biomedical Research Centre, Cambridge CB2 0QQ, UK.
Maelle MairesseClinical Pharmacology and Safety Sciences, AstraZeneca R&D, Cambridge CB4 0WG, UK.
Adrian Baez-OrtegaWellcome Sanger Institute, Wellcome Genome Campus, Hinxton CB10 1SA, UK.
Julia JonesCancer Research UK Cambridge Institute, Cambridge CB2 0AW, UK.
Thomas TanDepartment of Surgery, University of Cambridge and NIHR Cambridge Biomedical Research Centre, Cambridge CB2 0QQ, UK.
Sylvia RehakovaDepartment of Surgery, University of Cambridge and NIHR Cambridge Biomedical Research Centre, Cambridge CB2 0QQ, UK.
Krishnaa T MahbubaniDepartment of Surgery, University of Cambridge and NIHR Cambridge Biomedical Research Centre, Cambridge CB2 0QQ, UK.
Cara BrodieCancer Research UK Cambridge Institute, Cambridge CB2 0AW, UK.
Namshik HanMilner Therapeutics Institute, University of Cambridge, Cambridge CB2 0AW, UK; Cambridge Centre for AI in Medicine, University of Cambridge, Cambridge CB2 0XY, UK; Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 0AW, UK.
Inigo MartincorenaWellcome Sanger Institute, Wellcome Genome Campus, Hinxton CB10 1SA, UK.
Catherine BettsClinical Pharmacology and Safety Sciences, AstraZeneca R&D, Cambridge CB4 0WG, UK.
Ludovic VallierBerlin Institute of Health, Center for Regenerative Therapies, 13353 Berlin, Germany; Max-Planck-Institute for Molecular Genetics, 14195 Berlin, Germany.
Kourosh Saeb-ParsyDepartment of Surgery, University of Cambridge and NIHR Cambridge Biomedical Research Centre, Cambridge CB2 0QQ, UK. Electronic address: ks10014@cam.ac.uk.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Primary human cells cultured in long-term expandable 3D organoid format have great promise as potential regenerative cellular therapies, but their immunogenicity has not yet been fully characterized. In this study, we use in vitro co-cultures and in vivo humanized mouse experimental models to examine autologous and allogeneic immune response to human primary cholangiocyte organoids (PCOs) as treatment for bile duct disorders. Our data demonstrate that PCOs upregulate the expression of human leukocyte antigen (HLA)-I and HLA-II in inflammatory conditions. The allogeneic immune response to PCOs is driven by both HLA-I and HLA-II and is substantially ameliorated by donor-recipient HLA matching. While allogeneic cells display evolving stages of immune rejection in vivo, autologous PCOs induce a low-level immune infiltration into the graft site possibly influenced by acquired mutations in culture, cell viability, and culture matrix. Our findings have important implications for the design and clinical translation of autologous and allogeneic organoid cellular therapies.

Indexed as

Allogeneic CellsBile DuctsCell- and Tissue-Based TherapyOrganoidsAnimalsCells, CulturedCoculture TechniquesFemaleHumansMiceTransplantation, AutologousTransplantation, Homologousautologous and allogeneic immunogenicitycell therapiescholangiocytehumanized mouse modelhuman primary organoidsNanoSeqspatial transcriptomicstransplantation immunology

Identifiers

PMID40628261
PMCPMC12281383

What OpenQuestion holds

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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.