Evidence map›Paper›PMID 31276558›Full record

ArticlePloS one2019

Maturation of three-dimensional, hiPSC-derived cardiomyocyte spheroids utilizing cyclic, uniaxial stretch and electrical stimulation.

Wesley LaBarge, Saidulu Mattappally, Ramaswamy Kannappan, Vladimir G Fast, Daniëlle Pretorius, Joel L Berry, Jianyi Zhang

Erratum issuedAbstract read
In one paragraph

Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 59 papers.

0numbers the graph read from it
0cells of the map it votes in
59citing 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

59 citing papers in PubMed.

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  15. Novel, low-cost bioreactor forFrontiers in bioengineering and biotechnology · 2025
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors.

Wesley LaBargeDepartment of Biomedical Engineering, The University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
Saidulu MattappallyDepartment of Biomedical Engineering, The University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
Ramaswamy KannappanDepartment of Biomedical Engineering, The University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
Vladimir G FastDepartment of Biomedical Engineering, The University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
Daniëlle PretoriusDepartment of Biomedical Engineering, The University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
Joel L BerryDepartment of Biomedical Engineering, The University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
Jianyi ZhangDepartment of Biomedical Engineering, The University of Alabama at Birmingham, Birmingham, Alabama, United States of America.ORCID 0000-0002-3955-6554

Funding

Integrated Cellular and Tissue Engineering for Ischemic Heart DiseaseU01HL134764 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI BURSAC, NENAD, KAMP, TIMOTHY J. · 2016 to 2022
$7.7M
Supplement of HL131017: Myocardial remuscularization by cardiac patch delivery of epicardial FSTL1 and CCND2 overexpressing cardiomyocytesR01HL131017 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI SERPOOSHAN, VAHID, ZHANG, JIANYI · 2016 to 2025
$5.8M
Endogenous and exogenous mechanisms that promote myocardial remuscularization in post infarction LV remodelingR01HL114120 · NHLBI · UNIVERSITY OF MINNESOTA · PI ZHANG, JIANYI · 2012 to 2021
$5.6M
Development and Functional Assessment of Cardiovascular Tissue Engineering Therapy (CVTE) T32 Training GrantT32EB023872 · NIBIB · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI ROGERS, JACK M, ZHANG, JIANYI · 2018 to 2022
$753k
NHLBI NIH HHS R01 HL114120NHLBI NIH HHS R01 HL131017NHLBI NIH HHS U01 HL134764NIBIB NIH HHS T32 EB023872
6 · The paper itself

Abstract

Functional myocardium derived from human induced pluripotent stem cells (hiPSCs) can be impactful for cardiac disease modeling, drug testing, and the repair of injured myocardium. However, when hiPSCs are differentiated into cardiomyocytes, they do not possess characteristics of mature myocytes which limits their application in these endeavors. We hypothesized that mechanical and electrical stimuli would enhance the maturation of hiPSC-derived cardiomyocyte (hiPSC-CM) spheroids on both a structural and functional level, potentially leading to a better model for drug testing as well as cell therapy. Spheroids were generated with hiPSC-CM. For inducing mechanical stimulation, they were placed in a custom-made device with PDMS channels and exposed to cyclic, uniaxial stretch. Spheroids were electrically stimulated in the C-Pace EP from IONOptix for 7 days. Following the stimulations, the spheroids were then analyzed for cardiomyocyte maturation. Both stimulated groups of spheroids possessed enhanced transcript and protein expressions for key maturation markers, such as cTnI, MLC2v, and MLC2a, along with improved ultrastructure of the hiPSC-CMs in both groups with enhanced Z-band/Z-body formation, fibril alignment, and fiber number. Optical mapping showed that spheroids exposed to electrical stimulation were able to capture signals at increasing rates of pacing up to 4 Hz, which failed in unstimulated spheroids. Our results clearly indicate that a significantly improved myocyte maturation can be achieved by culturing iPSC-CMs as spheroids and exposing them to cyclic, uniaxial stretch and electrical stimulation.

Identifiers

PMID31276558
PMCPMC6611624

What Socratic holds

Textmetadata
LicenceCC BY
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.