Evidence map›Paper›PMID 42613640›Full record

ArticleStem cell research & therapy2026

Efficacy of multi-layered human iPS cell-derived cardiovascular cell sheets in a pacing-induced canine dilated cardiomyopathy model.

Yu Shimoyama, Kenji Kakuta, Kiho Araki, Hyoe Komae, Minoru Ono, Jun K Yamashita

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Article in Stem cell research & therapy, 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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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Yu ShimoyamaiHeart Japan Corporation, Kyoto, Japan.
Kenji KakutaiHeart Japan Corporation, Kyoto, Japan. info@iheartjapan.jp.
Kiho ArakiiHeart Japan Corporation, Kyoto, Japan.
Hyoe KomaeDepartment of Cardiovascular Surgery, The University of Tokyo Hospital, Tokyo, Japan.
Minoru OnoDepartment of Cardiovascular Surgery, The University of Tokyo Hospital, Tokyo, Japan.
Jun K YamashitaDepartment of Cellular and Tissue Communications, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. juny@m.u-tokyo.ac.jp.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDilated cardiomyopathy (DCM) is a progressive, intractable disease that leads to heart failure. Heart transplantation is the only curative treatment; however, access is limited by donor scarcity. Induced pluripotent stem cell (iPSC)-based therapies are attracting attention for DCM, but suitable large-animal models and robust preclinical data have been limited.

methodsWe generated multi-layered cardiovascular cell sheets from human iPSCs by combining cardiomyocytes with endothelial and stromal cells and overcoming stacking limits using interleaved gelatin hydrogel microspheres, yielding a thicker cardiac tissue-like construct (product code: IHJ-301). To enable rigorous testing in non-ischemic heart failure, we established a modified canine rapid-pacing heart failure model that maintains depressed function without mortality by continuing pacing at a slightly reduced rate after induction (Step-Down Pacing Heart Failure model). IHJ-301 was implanted epicardially onto the left ventricular surface via thoracotomy, and cardiac function was assessed by echocardiography and right-heart catheterization.

resultsAfter 4 weeks of rapid pacing (230 ± 10 bpm), left ventricular ejection fraction (LVEF) was reduced from 77.8 ± 1.1% (pre-pacing) to 44.9 ± 1.9% (n = 11) (0 W). Continued pacing at 210 ± 10 bpm for additional 4 weeks resulted in no mortality and maintained depressed function (4 W LVEF 47.3 ± 2.6%). IHJ-301 was implanted at 0 W. At 4 weeks post-implantation (4 W), all animals in the IHJ-301 group (n = 5) showed greater functional improvement than sham (n = 6). Absolute changes from 0 W to 4 W were: ΔLVEF (%) 9.38 ± 1.47 vs. 1.90 ± 0.34; Δfractional shortening (%) 4.84 ± 0.75 vs. 0.97 ± 0.18; stroke volume (mL/beat) 1.21 ± 1.26 vs. -2.99 ± 0.60; cardiac output (L/min) 0.19 ± 0.19 vs. -0.58 ± 0.12 (all p < 0.05).

conclusionsWe established a non-ischemic large-animal heart failure model that sustains depressed function for one month, enabling clear therapeutic readouts. IHJ-301 significantly improved multiple parameters of cardiac function, providing preclinical evidence that IHJ-301 could offer a promising therapeutic option for DCM.

Indexed as

Cardiomyopathy, DilatedInduced Pluripotent Stem CellsMyocytes, CardiacAnimalsDisease Models, AnimalDogsHeart FailureHumansBiomaterialDilated cardiomyopathyGelatin hydrogelHeart failureHuman induced pluripotent stem cellRegenerative therapy

Identifiers

PMID42613640
PMCPMC13488229

What Socratic 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 Socratic graph.