Human iPSC-derived engineered heart tissue model of diastolic dysfunction in heart failure with preserved ejection fraction

Hidenori Tani; Kotaro Haga; Taijun Moriwaki; Uikyu Bang; Shohei Fujii; Daichi Sekiguchi; Yuki Yamamoto; Kuniko Momoi; Masatoshi Ohno; Masashi Nakamura; Tomohiko C. Umei; Yuika Morita-Umei; Yusuke Soma; Yoshikazu Kishino; Motoaki Sano; Keiichi Fukuda; Akitsu Hotta; Masaki Ieda; Shugo Tohyama

doi:10.1016/j.stem.2026.06.007

Human iPSC-derived engineered heart tissue model of diastolic dysfunction in heart failure with preserved ejection fraction

Hidenori Tani
, Kotaro Haga
, Taijun Moriwaki
, Uikyu Bang
, Shohei Fujii
, Daichi Sekiguchi
, Yuki Yamamoto
, Kuniko Momoi
, Masatoshi Ohno
, Masashi Nakamura
, Tomohiko C. Umei
, Yuika Morita-Umei
, Yusuke Soma
, Yoshikazu Kishino
, Motoaki Sano
, Keiichi Fukuda
, Akitsu Hotta
, Masaki Ieda
, Shugo Tohyama

Research output: Contribution to journal › Article › peer-review

1 Citation (Scopus)

Abstract

Tohyama and colleagues successfully established an in vitro diastolic dysfunction model that mimics HFpEF using hiPSC-derived heart tissues and demonstrated the therapeutic efficacy of SGLT2 inhibitors. Furthermore, they revealed that the restoration of the eNOS-NO-cGMP-PKG signaling pathway in endothelial cells plays a crucial role in ameliorating heart failure.

Original language	English
Pages (from-to)	1339-1353.e7
Journal	Cell Stem Cell
Volume	33
Issue number	8
DOIs	https://doi.org/10.1016/j.stem.2026.06.007
Publication status	Published - 06-08-2026

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

All Science Journal Classification (ASJC) codes

Molecular Medicine
Genetics
Cell Biology

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10.1016/j.stem.2026.06.007

Cite this

Tani, H., Haga, K., Moriwaki, T., Bang, U., Fujii, S., Sekiguchi, D., Yamamoto, Y., Momoi, K., Ohno, M., Nakamura, M., Umei, T. C., Morita-Umei, Y., Soma, Y., Kishino, Y., Sano, M., Fukuda, K., Hotta, A., Ieda, M., & Tohyama, S. (2026). Human iPSC-derived engineered heart tissue model of diastolic dysfunction in heart failure with preserved ejection fraction. Cell Stem Cell, 33(8), 1339-1353.e7. https://doi.org/10.1016/j.stem.2026.06.007

@article{e7778989d47f4dce8a6ea7456897dec8,

title = "Human iPSC-derived engineered heart tissue model of diastolic dysfunction in heart failure with preserved ejection fraction",

abstract = "Tohyama and colleagues successfully established an in vitro diastolic dysfunction model that mimics HFpEF using hiPSC-derived heart tissues and demonstrated the therapeutic efficacy of SGLT2 inhibitors. Furthermore, they revealed that the restoration of the eNOS-NO-cGMP-PKG signaling pathway in endothelial cells plays a crucial role in ameliorating heart failure.",

keywords = "diastolic dysfunction, drug discovery, engineered heart tissue, eNOS-NO-cGMP-PKG signaling pathway, heart failure with preserved ejection fraction, HFpEF, human induced pluripotent stem cells, SGLT2i, sodium-glucose cotransporter 2 inhibitor",

author = "Hidenori Tani and Kotaro Haga and Taijun Moriwaki and Uikyu Bang and Shohei Fujii and Daichi Sekiguchi and Yuki Yamamoto and Kuniko Momoi and Masatoshi Ohno and Masashi Nakamura and Umei, \{Tomohiko C.\} and Yuika Morita-Umei and Yusuke Soma and Yoshikazu Kishino and Motoaki Sano and Keiichi Fukuda and Akitsu Hotta and Masaki Ieda and Shugo Tohyama",

note = "Publisher Copyright: {\textcopyright} 2026 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license. http://creativecommons.org/licenses/by/4.0/",

year = "2026",

month = aug,

day = "6",

doi = "10.1016/j.stem.2026.06.007",

language = "English",

volume = "33",

pages = "1339--1353.e7",

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Tani, H, Haga, K, Moriwaki, T, Bang, U, Fujii, S, Sekiguchi, D, Yamamoto, Y, Momoi, K, Ohno, M, Nakamura, M, Umei, TC, Morita-Umei, Y, Soma, Y, Kishino, Y, Sano, M, Fukuda, K, Hotta, A, Ieda, M & Tohyama, S 2026, 'Human iPSC-derived engineered heart tissue model of diastolic dysfunction in heart failure with preserved ejection fraction', Cell Stem Cell, vol. 33, no. 8, pp. 1339-1353.e7. https://doi.org/10.1016/j.stem.2026.06.007

TY - JOUR

T1 - Human iPSC-derived engineered heart tissue model of diastolic dysfunction in heart failure with preserved ejection fraction

AU - Tani, Hidenori

AU - Haga, Kotaro

AU - Moriwaki, Taijun

AU - Bang, Uikyu

AU - Fujii, Shohei

AU - Sekiguchi, Daichi

AU - Yamamoto, Yuki

AU - Momoi, Kuniko

AU - Ohno, Masatoshi

AU - Nakamura, Masashi

AU - Umei, Tomohiko C.

AU - Morita-Umei, Yuika

AU - Soma, Yusuke

AU - Kishino, Yoshikazu

AU - Sano, Motoaki

AU - Fukuda, Keiichi

AU - Hotta, Akitsu

AU - Ieda, Masaki

AU - Tohyama, Shugo

PY - 2026/8/6

Y1 - 2026/8/6

N2 - Tohyama and colleagues successfully established an in vitro diastolic dysfunction model that mimics HFpEF using hiPSC-derived heart tissues and demonstrated the therapeutic efficacy of SGLT2 inhibitors. Furthermore, they revealed that the restoration of the eNOS-NO-cGMP-PKG signaling pathway in endothelial cells plays a crucial role in ameliorating heart failure.

AB - Tohyama and colleagues successfully established an in vitro diastolic dysfunction model that mimics HFpEF using hiPSC-derived heart tissues and demonstrated the therapeutic efficacy of SGLT2 inhibitors. Furthermore, they revealed that the restoration of the eNOS-NO-cGMP-PKG signaling pathway in endothelial cells plays a crucial role in ameliorating heart failure.

KW - diastolic dysfunction

KW - drug discovery

KW - engineered heart tissue

KW - eNOS-NO-cGMP-PKG signaling pathway

KW - heart failure with preserved ejection fraction

KW - HFpEF

KW - human induced pluripotent stem cells

KW - SGLT2i

KW - sodium-glucose cotransporter 2 inhibitor

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UR - https://www.scopus.com/pages/publications/105046308593#tab=citedBy

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DO - 10.1016/j.stem.2026.06.007

M3 - Article

C2 - 42462723

AN - SCOPUS:105046308593

SN - 1934-5909

VL - 33

SP - 1339-1353.e7

JO - Cell Stem Cell

JF - Cell Stem Cell

IS - 8

ER -

Human iPSC-derived engineered heart tissue model of diastolic dysfunction in heart failure with preserved ejection fraction

Abstract

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