Evidence map›Paper›PMID 40730607›Full record

ArticleScientific reports2025

Derivation of resident macrophages and construction of tumor microenvironment in Flk-1-knockout chimeric mice produced via blastocyst complementation.

Satoko Ishii, Kazuto Yamazaki, Peng Li, Kenji Kubara, Yuta Ishizuka, Yukina Izumi, Tsutomu Kamisako, Hiroyoshi Ishizaki, Yuichi Ono, Naoaki Mizuno and 5 more

Abstract read
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In one paragraph

Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

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

15 authors.

Satoko IshiiTsukuba Research Laboratories, Eisai Co., Ltd., 5-1-3, Tokodai, Tsukuba, Ibaraki, 300-2635, Japan. s4-ishii@hhc.eisai.co.jp.
Kazuto YamazakiTsukuba Research Laboratories, Eisai Co., Ltd., 5-1-3, Tokodai, Tsukuba, Ibaraki, 300-2635, Japan. k5-yamazaki@hhc.eisai.co.jp.
Peng LiTsukuba Research Laboratories, Eisai Co., Ltd., 5-1-3, Tokodai, Tsukuba, Ibaraki, 300-2635, Japan.
Kenji KubaraTsukuba Research Laboratories, Eisai Co., Ltd., 5-1-3, Tokodai, Tsukuba, Ibaraki, 300-2635, Japan.
Yuta IshizukaKobe Research Laboratories, Eisai Co., Ltd., 6-8-2 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo, 650-0047, Japan.
Yukina IzumiKobe Research Laboratories, Eisai Co., Ltd., 6-8-2 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo, 650-0047, Japan.
Tsutomu KamisakoKobe Research Laboratories, Eisai Co., Ltd., 6-8-2 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo, 650-0047, Japan.
Hiroyoshi IshizakiKobe Research Laboratories, Eisai Co., Ltd., 6-8-2 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo, 650-0047, Japan.
Yuichi OnoKobe Research Laboratories, Eisai Co., Ltd., 6-8-2 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo, 650-0047, Japan.
Naoaki MizunoStem Cell Therapy Division, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
Hideyuki SatoStem Cell Therapy Division, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
Hideki MasakiStem Cell Therapy Division, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
Motoo WatanabeStem Cell Therapy Division, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
Masashi ItoTsukuba Research Laboratories, Eisai Co., Ltd., 5-1-3, Tokodai, Tsukuba, Ibaraki, 300-2635, Japan.
Hiromitsu NakauchiStem Cell Therapy Division, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The tumor microenvironment (TME) is deeply involved in cancer progression and treatment resistance. Although humanized mouse models have been developed by transplanting human cells into immunodeficient mice, they fail to fully reconstitute the TME. Blastocyst complementation using Flk-1 (Vegfr2, Kdr) knockout hosts offers a potential solution. However, the generation of interspecies human-mouse chimeras using blastocyst complementation has not yet been successful. As a foundational step, this study aims to demonstrate that donor-derived TME can be constructed using this method in intraspecies chimeric mice. We generated chimeric mice by injecting Azami-Green (AG)-positive C57BL/6 (B6) mouse-derived embryonic stem cells (ESCs) into ICR Flk-1 knockout embryos. We observed that vascular endothelial cells (VECs), hematopoietic cells, and tissue-resident macrophages were derived from the injected AG-positive ESCs. We engrafted B6-derived tumor cells into the chimeras and identified tumor-infiltrating lymphocytes, tumor-associated macrophages, and VECs derived from donor cells. Moreover, tumor-infiltrating CD8

Indexed as

BlastocystMacrophagesTumor MicroenvironmentVascular Endothelial Growth Factor Receptor-2AnimalsChimeraDisease Models, AnimalEmbryonic Stem CellsEndothelial CellsHumansMiceMice, Inbred C57BLMice, KnockoutVascular Endothelial Growth Factor Receptor-2Blastocyst complementationResident macrophagesTumor microenvironmentTumor model

Identifiers

PMID40730607
PMCPMC12307763

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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.