Evidence map›Paper›PMID 32057252›Full record

ArticleAmerican journal of physiology. Heart and circulatory physiology2020

DNA damage-free iPS cells exhibit potential to yield competent cardiomyocytes.

Jessica M Miller, Nikhil M Mardhekar, Danielle Pretorius, Prasanna Krishnamurthy, Namakkal Soorappan Rajasekaran, Jianyi Zhang, Ramaswamy Kannappan

Open access · greenAbstract read
In one paragraph

Article in American journal of physiology. Heart and circulatory physiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.8field-weighted citation impact, top 29% of its field
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

3 citing papers in PubMed, 12 citations in OpenAlex.

  1. Article
  2. Article
  3. 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

7 authors at 1 institution in 1 country.

Jessica M MillerDepartment of Biomedical Engineering, School of Engineering, School of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama.
Nikhil M MardhekarDepartment of Biomedical Engineering, School of Engineering, School of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama.
Danielle PretoriusDepartment of Biomedical Engineering, School of Engineering, School of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama.
Prasanna KrishnamurthyDepartment of Biomedical Engineering, School of Engineering, School of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama.
Namakkal Soorappan RajasekaranDepartment of Biomedical Engineering, School of Engineering, School of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama.
Jianyi ZhangDepartment of Biomedical Engineering, School of Engineering, School of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama.
Ramaswamy KannappanDepartment of Biomedical Engineering, School of Engineering, School of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama.
University of Alabama at Birmingham · US

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
Reductive Stress Induces Proteotoxic Cardiac DiseaseR01HL118067 · NHLBI · UNIVERSITY OF UTAH · PI NAMAKKAL SOORAPPAN, RAJASEKARAN · 2013 to 2021
$4.5M
Stem Cells For Myocardial Repair: A Large Bore Magnet StudyR01HL095077 · NHLBI · UNIVERSITY OF MINNESOTA · PI ZHANG, JIANYI · 2009 to 2017
$3.8M
Deciphering the Neonatal Cardiac Regenerative Potential and Regulators in Large AnimalsR01HL149137 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI SADEK, HESHAM, ZANGI, LIOR · 2019 to 2022
$2.5M
NHLBI NIH HHS R01 HL095077NHLBI NIH HHS R01 HL118067NHLBI NIH HHS R01 HL131017NHLBI NIH HHS R01 HL149137NHLBI NIH HHS U01 HL134764
6 · The paper itself

Abstract

DNA damage accrued in induced pluripotent stem cell (iPSC)-derived cardiomyocytes during in vitro culture practices lessens their therapeutic potential. We determined whether DNA-damage-free iPSCs (DdF-iPSCs) can be selected using stabilization of p53, a transcription factor that promotes apoptosis in DNA-damaged cells, and differentiated them into functionally competent DdF cardiomyocytes (DdF-CMs). p53 was activated using Nutlin-3a in iPSCs to selectively kill the DNA-damaged cells, and the stable DdF cells were cultured further and differentiated into CMs. Both DdF-iPSCs and DdF-CMs were then characterized. We observed a significant decrease in the expression of reactive oxygen species and DNA damage in DdF-iPSCs compared with control (Ctrl) iPSCs. Next-generation RNA sequencing and Ingenuity Pathway Analysis revealed improved molecular, cellular, and physiological functions in DdF-iPSCs. The differentiated DdF-CMs had a compact beating frequency between 40 and 60 beats/min accompanied by increased cell surface area. Additionally, DdF-CMs were able to retain the improved molecular, cellular, and physiological functions after differentiation from iPSCs, and, interestingly, cardiac development network was prominent compared with Ctrl-CMs. Enhanced expression of various ion channel transcripts in DdF-CMs implies DdF-CMs are of ventricular CMs and mature compared with their counterparts. Our results indicated that DdF-iPSCs could be selected through p53 stabilization using a small-molecule inhibitor and differentiated into ventricular DdF-CMs with fine-tuned molecular signatures. These iPSC-derived DdF-CMs show immense clinical potential in repairing injured myocardium.

Indexed as

Cell DifferentiationDNA DamageCells, CulturedCellular Reprogramming TechniquesHumansInduced Pluripotent Stem CellsIon ChannelsMyocardial ContractionMyocytes, CardiacTumor Suppressor Protein p53Ion ChannelsTumor Suppressor Protein p53DNA damageiPS-CMiPSCsp53

Identifiers

PMID32057252
PMCPMC7276931
OpenAlexW3006283813

What OpenQuestion holds

Textmetadata
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 OpenQuestion graph.