Evidence map›Paper›PMID 41328308›Full record

ArticleCellular and molecular bioengineering2025

Disrupted Sarcomere Reorganization of Cardiomyopathy-Prone Human iPSC-Derived Cardiomyocytes on a Dynamic Mechanical Substrate.

Nhu Y Mai, Xiangjun Wu, Huiyao Liu, Ariel Ash-Shakoor, Huaiyu Shi, Zhuocheng Qu, Patrick T Mather, Xinrui Wang, James H Henderson, Zhen Ma

Abstract read
In one paragraph

Article in Cellular and molecular bioengineering, 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. 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

10 authors.

Nhu Y Mai *Department of Biomedical and Chemical Engineering, Syracuse University, 318 Bowne Hall, Syracuse, NY 13244 USA.
Xiangjun Wu *Department of Biomedical and Chemical Engineering, Syracuse University, 318 Bowne Hall, Syracuse, NY 13244 USA.
Huiyao LiuDepartment of Biomedical and Chemical Engineering, Syracuse University, 318 Bowne Hall, Syracuse, NY 13244 USA.
Ariel Ash-ShakoorDepartment of Biomedical and Chemical Engineering, Syracuse University, 318 Bowne Hall, Syracuse, NY 13244 USA.
Huaiyu ShiDepartment of Biomedical and Chemical Engineering, Syracuse University, 318 Bowne Hall, Syracuse, NY 13244 USA.
Zhuocheng QuDepartment of Pharmacology, SUNY Upstate Medical University, Syracuse, NY USA.
Patrick T MatherDepartment of Chemical Engineering, Penn State University, University Park, PA USA.
Xinrui WangDepartment of Pharmacology, SUNY Upstate Medical University, Syracuse, NY USA.
James H HendersonDepartment of Biomedical and Chemical Engineering, Syracuse University, 318 Bowne Hall, Syracuse, NY 13244 USA.
Zhen MaDepartment of Biomedical and Chemical Engineering, Syracuse University, 318 Bowne Hall, Syracuse, NY 13244 USA.ORCID 0000-0001-5228-105X

Funding

Establishing an In Vitro Embryotoxicity Risk Classification System Based on Human Cardiac Organoid ModelR01HD101130 · NICHD · SYRACUSE UNIVERSITY · PI MA, ZHEN · 2020 to 2025
$2.3M
NICHD NIH HHS R01 HD101130
6 · The paper itself

Abstract

Introduction: Approximately 15% of dilated cardiomyopathy (DCM) cases are associated with Bcl2-associated athanogene 3 (BAG3) gene mutations, which play a crucial role in myofilament organization and contractile behavior. Previous studies have highlighted the role of dynamic mechanical stress in myofibril alignment in human-induced pluripotent stem cell-derived cardiomyocytes (hiPSCCMs). In this study, we employed thermo-responsive shape memory polymers (SMPs) to mimic the dynamic mechanical environment of the extracellular matrix (ECM) and investigated their impact on myofibril assembly in healthy wild-type (WT) and BAG3 knockout (BAG3-/-) hiPSC-CMs. Methods: We synthesized Tert-Butyl Acrylate (TBA) and Butyl acrylate (BA)-based SMP substrate. hiPSC-CMs were cultured on 30oC on 40% strained (dynamic) and un-strain (static) SMPs for two days before proceeding with polymer recovery at 37oC. Myofibril components of BAG3 knock-out (KO) and WT CMs were evaluated by immunocytochemistry fluorescent images at 5 hours and 24 hours after triggering the shape changes of the SMP substrate. We quantified Z-lines and M-lines of hiPSC-CMs to evaluate sarcomere remodeling on static and dynamic substrates. Results: Our findings revealed that BAG3-/- hiPSC-CMs exhibited persistent Z-line disruption in sarcomeres compared with WT hiPSC-CMs, but M-line structures were less sensitive to mechanical stress at 5 hours, highlighted a temporal distinction in the assembly and regulation of Z-lines over M-lines. While no significant changes were detected at 5 hours, BAG3-/- CMs exhibited similar impairments in M-line organization as seen with Z-lines. These findings suggest that M-lines in BAG3-/- CMs display heightened sensitivity to dynamic mechanical actuation, but this phenotype emerges only after prolonged culture. Conclusions: This study highlights the interplay between genetic deficiency and mechanical stress to facilitate disease progression in BAG3-associated DCM. Supplementary Information: The online version contains supplementary material available at 10.1007/s12195-025-00880-z.

Indexed as

Active biomaterialsDisease modelingDynamic mechanobiologyHuman induced pluripotent stem cells

Identifiers

PMID41328308
PMCPMC12664868

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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.