Evidence map›Paper›PMID 41165859›Full record

ArticleCellular and molecular life sciences : CMLS2025

Modeling myocardial physiological growth using human pluripotent stem cell derived cardiomyocytes and 3D cardiac microtissues.

Chang Liu, Jianhua Yao, Xinying Wu, Jing Guo, Qingyi Zhan, Yujiao Zhu, Emeli Chatterjee, Tarun Keswani, Danni Meng, Guoping Li and 4 more

Abstract read
In one paragraph

Article in Cellular and molecular life sciences : CMLS, 2025. 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

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

14 authors.

Chang Liu *Institute of Geriatrics (Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong) and School of Life Sciences, Shanghai University, Nantong, 226011, China.
Jianhua Yao *Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.
Xinying Wu *Institute of Geriatrics (Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong) and School of Life Sciences, Shanghai University, Nantong, 226011, China.
Jing GuoInstitute of Geriatrics (Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong) and School of Life Sciences, Shanghai University, Nantong, 226011, China.
Qingyi ZhanInstitute of Geriatrics (Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong) and School of Life Sciences, Shanghai University, Nantong, 226011, China.
Yujiao ZhuInstitute of Geriatrics (Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong) and School of Life Sciences, Shanghai University, Nantong, 226011, China.
Emeli ChatterjeeCardiovascular Division of the Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
Tarun KeswaniCenter for Immunological and Inflammatory Diseases, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02129, USA.
Danni MengInstitute of Geriatrics (Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong) and School of Life Sciences, Shanghai University, Nantong, 226011, China.
Guoping LiCardiovascular Division of the Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
Dragos CretoiuDepartment of Medical Genetics, Carol Davila University of Medicine and Pharmacy, 020031, Bucharest, Romania.
Anthony RosenzweigStanley and Judith Frankel Institute for Heart and Brain Health, University of Michigan Medical Center, Ann Arbor, MI, 48109, USA.
Yihua BeiInstitute of Geriatrics (Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong) and School of Life Sciences, Shanghai University, Nantong, 226011, China. beiyh36@shu.edu.cn.
Junjie XiaoInstitute of Geriatrics (Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong) and School of Life Sciences, Shanghai University, Nantong, 226011, China. junjiexiao@shu.edu.cn.ORCID http://orcid.org/0000-0002-9202-0003

Funding

"Dawn" Program of Shanghai Education Commission 24SG36National Key R&D Program of China 2022YFA1104500National Natural Science Foundation of China 82020108002National Natural Science Foundation of China 82170285National Natural Science Foundation of China 82225005National Natural Science Foundation of China 82370285National Natural Science Foundation of China 82470275Oriental Scholars of Shanghai Universities TP2022057Science and Technology Commission of Shanghai Municipality 23010500300Science and Technology Commission of Shanghai Municipality 23410750100
6 · The paper itself

Abstract

Cardiac physiological growth is needed for increased demands of heart function after exercise. Prior work suggests that exercise-responsive molecules, including Cbp/P300 Interacting Transactivator with Glu/Asp Rich Carboxy-Terminal Domain 4 (CITED4), can mediate exercise-induced myocardial physiological growth and promote functional recovery after ischemia-reperfusion injury in adult mice. Moreover, forced expression of CITED4 induces physiological cardiac growth in rodent model. Multiple mouse models of myocardial physiological growth have been established by activating genes such as CITED4, IGF1R and AKT. However, an in vitro model of physiological growth in cardiomyocytes derived from human embryonic stem cells (hESC-CMs) has not yet been developed. To provide clinically relevant models for exploring the molecular mechanism of physiological growth, we generated an inducible hESC cell line with forced CITED4 gene expression and differentiated those hESCs towards cardiomyocytes. The results showed that forced CITED4 expression increased cell size and proliferation in hESC-CMs, and promoted cardiomyocyte proliferation in 3D cardiac microtissues. Activation of protein kinase B (also known as AKT1) signaling was necessary for CITED4-induced proliferation in hESC-CMs and 3D cardiac microtissues, while mTOR signaling mediated both proliferation and physiological hypertrophy induced by CITED4. In an in vitro model mimicking ischemia-reperfusion injury, CITED4 expression inhibited cardiomyocyte apoptosis in hESC-CMs and 3D cardiac microtissues, and this effect was mediated by activation of the mTOR signaling. In conclusion, we successfully generate a physiological growth model in hESC-CMs and 3D cardiac microtissues. Moreover, physiological growth induced by CITED4 is mediated by activation of the mTOR signaling, which is necessary to promote both proliferation and physiological hypertrophy, and to alleviate apoptosis after ischemia-reperfusion injury in hESC-CMs and 3D cardiac microtissues.

Indexed as

Cardiomegaly, Exercise-InducedCell Culture Techniques, Three DimensionalHeartMyocardiumMyocytes, CardiacPluripotent Stem CellsApoptosisCardiomegalyCell ProliferationHumansReperfusion InjuryTOR Serine-Threonine KinasesTranscription FactorsCITED4 protein, humanMTOR protein, humanTOR Serine-Threonine KinasesTranscription FactorsAKTCardiac microtissueCITED4Embryonic stem cellsIschemia–reperfusion injurymTORMyocardial physiological growth

Identifiers

PMID41165859
PMCPMC12575888

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

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 Socratic graph.