Evidence map›Paper›PMID 42248141›Full record

ArticleCell2026

Xenophagocytosis blockade enhances interspecies chimerism.

Sicong Wang, Kouta Niizuma, Daniel Dan Liu, Fabian P Suchy, Alyssa H Chang, Saman Tabatabaee, Hideyuki Sato, Ayaka Yanagida, Hideki Masaki, Nathan Hidajat and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2026. 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. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors.

Sicong WangInstitute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Kouta NiizumaInstitute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Daniel Dan LiuInstitute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Fabian P SuchyInstitute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Alyssa H ChangInstitute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Saman TabatabaeeInstitute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Hideyuki SatoStem Cell Therapy Laboratory, Institute of Integrated Research, Institute of Science, Tokyo, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
Ayaka YanagidaDepartment of Veterinary Anatomy, The University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-8657, Japan.
Hideki MasakiStem Cell Therapy Laboratory, Institute of Integrated Research, Institute of Science, Tokyo, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
Nathan HidajatInstitute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Shota HommaInstitute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Masashi MiyauchiInstitute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Joydeep BhaduryInstitute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Carsten T CharlesworthInstitute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Jinyu ZhangInstitute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Irving L WeissmanInstitute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Hiromitsu NakauchiInstitute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA; Stem Cell Therapy Laboratory, Institute of Integrated Research, Institute of Science, Tokyo, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan. Electronic address: nakauchi@stanford.edu.

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007365 · NIGMS · STANFORD UNIVERSITY · PI CHUA, KATRIN F · 1985 to 2021
$33.8M
Medical Scientist Training ProgramT32GM145402 · NIGMS · STANFORD UNIVERSITY · PI Katrin F. Chua · 2022 to 2026
$10.0M
Stem Cell Biology, Cancer Stem Cell Biology, and Cancer ImmunotherapyR35CA220434 · NCI · STANFORD UNIVERSITY · PI WEISSMAN, IRVING L. · 2017 to 2023
$6.7M
Understanding the developmental xenobarrierR01DK121851 · NIDDK · STANFORD UNIVERSITY · PI NAKAUCHI, HIROMITSU · 2020 to 2022
$1.2M
Selectable non-mosaic embryo editingR21OD030009 · OD · STANFORD UNIVERSITY · PI NAKAUCHI, HIROMITSU · 2020 to 2021
$444k
NCI NIH HHS R35 CA220434NIDDK NIH HHS R01 DK121851NIGMS NIH HHS T32 GM007365NIGMS NIH HHS T32 GM145402NIH HHS R21 OD030009
6 · The paper itself

Abstract

Organ shortage remains a major challenge in transplantation medicine. Interspecies blastocyst complementation offers a promising strategy to generate human organs in livestock. However, efficient xenogeneic donor cell engraftment remains challenging. Here, we identify an innate immune barrier wherein host macrophages selectively eliminate viable xenogeneic donor cells, a process we term xenophagocytosis. Mechanistically, xenogeneic cells display elevated phosphatidylserine, an "eat-me" signal recognized by host macrophages through phagocytic receptor Axl. We demonstrate three orthogonal strategies for xenophagocytosis blockade: genetic ablation of macrophages or the Axl receptor in the host embryo or overexpression of the "don't-eat-me" signal CD47 or the phosphatidylserine-regulating flippase ATP11C in donor cells. Xenophagocytosis blockade enhances rat and human donor chimerism in mouse embryos and improves interspecies pancreas complementation efficiency. These findings reveal a previously unrecognized innate immune barrier that safeguards species integrity during early embryogenesis and provide mechanistic insights to enhance xenogeneic chimerism for generating human organs in livestock.

Indexed as

ChimerismPhagocytosisAnimalsFemaleHumansImmunity, InnateMacrophagesMiceMice, Inbred C57BLPhosphatidylserinesRatsReceptor Protein-Tyrosine KinasesTransplantation, HeterologousPhosphatidylserinesReceptor Protein-Tyrosine Kinasesblastocyst complementationdevelopmental quality controlexogenic organogenesisinnate immune responseinterspecies chimerasinterspecies organogenesismacrophagepancreas reconstructionphagoptosisphosphatidylserine-regulating flippasexenogeneic barrier

Identifiers

PMID42248141
PMCPMC13361098

What OpenQuestion holds

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Registered trials

None linked

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.