Evidence map›Paper›PMID 41202806›Full record

ArticleCell reports. Medicine2025

Modeling antithymocyte globulin-induced microvasculopathy using human iPSC-derived vascularized liver organoids.

Shuntaro Kawamura, Yosuke Yoneyama, Norikazu Saiki, Yunheng Wu, Chiharu Moriya, Rio Ohmura, Mari Maezawa, Yoshihiro Shimada, Yicheng Wang, Kensaku Mori and 6 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 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. 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

16 authors.

Shuntaro KawamuraHuman Biology Research Unit, Institute of Integrated Research, Institute of Science Tokyo (Science Tokyo), 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
Yosuke YoneyamaHuman Biology Research Unit, Institute of Integrated Research, Institute of Science Tokyo (Science Tokyo), 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510, Japan; Department of Genome Biology, Graduate School of Medicine, and Premium Research Institute for Human Metaverse Medicine (WPI-PRIMe), the University of Osaka, Suita, Osaka 565-0871, Japan.
Norikazu SaikiHuman Biology Research Unit, Institute of Integrated Research, Institute of Science Tokyo (Science Tokyo), 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510, Japan; Organoid Medicine Project, T-CiRA Joint Program, Fujisawa, Kanagawa 251-8555, Japan.
Yunheng WuGraduate School of Informatics, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
Chiharu MoriyaDepartment of Genome Biology, Graduate School of Medicine, and Premium Research Institute for Human Metaverse Medicine (WPI-PRIMe), the University of Osaka, Suita, Osaka 565-0871, Japan.
Rio OhmuraHuman Biology Research Unit, Institute of Integrated Research, Institute of Science Tokyo (Science Tokyo), 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510, Japan; Organoid Medicine Project, T-CiRA Joint Program, Fujisawa, Kanagawa 251-8555, Japan.
Mari MaezawaHuman Biology Research Unit, Institute of Integrated Research, Institute of Science Tokyo (Science Tokyo), 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
Yoshihiro ShimadaHuman Biology Research Unit, Institute of Integrated Research, Institute of Science Tokyo (Science Tokyo), 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
Yicheng WangGraduate School of Informatics, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
Kensaku MoriGraduate School of Informatics, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan; Information Technology Center, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan; Research Center for Medical Bigdata, National Institute of Informatics, Tokyo 100-0003, Japan.
Noriki OkadaDivision of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University, Shimotsuke, Tochigi 329-0431, Japan.
Yasuharu OnishiDivision of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University, Shimotsuke, Tochigi 329-0431, Japan.
Yukihiro SanadaDivision of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University, Shimotsuke, Tochigi 329-0431, Japan.
Yuta HirataDivision of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University, Shimotsuke, Tochigi 329-0431, Japan.
Yasunaru SakumaDivision of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University, Shimotsuke, Tochigi 329-0431, Japan.
Takanori TakebeHuman Biology Research Unit, Institute of Integrated Research, Institute of Science Tokyo (Science Tokyo), 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510, Japan; Department of Genome Biology, Graduate School of Medicine, and Premium Research Institute for Human Metaverse Medicine (WPI-PRIMe), the University of Osaka, Suita, Osaka 565-0871, Japan; Organoid Medicine Project, T-CiRA Joint Program, Fujisawa, Kanagawa 251-8555, Japan; Division of Gastroenterology, Hepatology and Nutrition & Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229-3039, USA; The Center for Stem Cell and Organoid Medicine (CuSTOM), Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229- 3039, USA; Department of Pediatrics, University of Cincinnati College of Medicine, 3333 Burnet Avenue, Cincinnati, OH 45229-3039, USA; Communication Design Center, Advanced Medical Research Center, Yokohama City University, Yokohama, Kanagawa, Japan. Electronic address: takanori.takebe@cchmc.org.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Antithymocyte globulin (ATG) is a widely used immunosuppressive agent, yet its off-target vascular effects remain a clinical challenge in part due to a lack of relevant human models. Here, we uncover a biphasic mechanism of ATG-induced microvasculopathy using a humanized liver organoid platform derived from induced pluripotent stem cells (iPSCs). We show that ATG triggers a rapid, complement-dependent phase of injury restricted to human iPSC-derived liver sinusoidal endothelial cells (iLSECs), leading to C3 deposition and acute thrombosis specifically in human but not in mouse vessels. Transcriptomics reveals a delayed transforming growth factor β (TGF-β) pathway-driven proinflammatory program that coincides with neutrophil recruitment and degranulation, while pharmacological TGF-β blockade attenuates thrombosis and flow disturbance. Our findings reveal a pathogenic sequence of complement and TGF-β pathway activation and establish a translational platform for dissecting human liver-specific microvasculopathy in vivo.

Indexed as

Antilymphocyte SerumHepatic Veno-Occlusive DiseaseImmunosuppressive AgentsLiverMicrovesselsThrombosisAdultAnimalsCell LineComplement C3Endothelial CellsFemaleGraft RejectionHumansInduced Pluripotent Stem CellsLiver TransplantationAntilymphocyte SerumComplement C3Immunosuppressive AgentsTransforming Growth Factor betaATGcomplementimmunothrombosisinduced pluripotent stem cellintravital imagingliver sinusoidal endothelial cellmicrovasculopathyorganoidSOSTGF-β

Identifiers

PMID41202806
PMCPMC12711670

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.