Evidence map›Paper›PMID 25082575›Full record

ArticleJournal of the American College of Cardiology2014

Effect of human donor cell source on differentiation and function of cardiac induced pluripotent stem cells.

Veronica Sanchez-Freire, Andrew S Lee, Shijun Hu, Oscar J Abilez, Ping Liang, Feng Lan, Bruno C Huber, Sang-Ging Ong, Wan Xing Hong, Mei Huang and 1 more

Abstract readComparative Study
In one paragraph

Article in Journal of the American College of Cardiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.

0numbers the graph read from it
0cells of the map it votes in
70citing papers in PubMed
7.8field-weighted citation impact, top 2% 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

70 citing papers in PubMed, 124 citations in OpenAlex.

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10 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 2 institutions in 1 country.

Veronica Sanchez-FreireDepartment of Medicine, Division of Cardiology, Stanford University School of Medicine, Stanford, California; Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California; Department of Radiology, Stanford University School of Medicine, Stanford, California; Institute of Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California.
Andrew S LeeDepartment of Medicine, Division of Cardiology, Stanford University School of Medicine, Stanford, California; Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California; Institute of Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California.
Shijun HuDepartment of Medicine, Division of Cardiology, Stanford University School of Medicine, Stanford, California; Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California; Institute of Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California.
Oscar J AbilezStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California.
Ping LiangDepartment of Medicine, Division of Cardiology, Stanford University School of Medicine, Stanford, California; Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California; Department of Radiology, Stanford University School of Medicine, Stanford, California.
Feng LanDepartment of Medicine, Division of Cardiology, Stanford University School of Medicine, Stanford, California; Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California; Department of Radiology, Stanford University School of Medicine, Stanford, California.
Bruno C HuberDepartment of Medicine, Division of Cardiology, Stanford University School of Medicine, Stanford, California; Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California.
Sang-Ging OngDepartment of Medicine, Division of Cardiology, Stanford University School of Medicine, Stanford, California; Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California; Department of Radiology, Stanford University School of Medicine, Stanford, California.
Wan Xing HongDepartment of Medicine, Division of Cardiology, Stanford University School of Medicine, Stanford, California; Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California; Institute of Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California.
Mei HuangDepartment of Medicine, Division of Cardiology, Stanford University School of Medicine, Stanford, California; Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California; Department of Radiology, Stanford University School of Medicine, Stanford, California.
Joseph C WuDepartment of Medicine, Division of Cardiology, Stanford University School of Medicine, Stanford, California; Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California; Department of Radiology, Stanford University School of Medicine, Stanford, California; Institute of Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California. Electronic address: joewu@stanford.edu.
Cardiovascular Institute of the South · USCalifornia Institute for Regenerative Medicine · US

Funding

Project 3: Effect of Age and Longevity Genes on Epigenomic MechanismsP01GM099130 · NIGMS · STANFORD UNIVERSITY · PI WEISSMAN, SHERMAN MORTON · 2011 to 2015
$11.4M
Biorepository of Human iPSCs for Studying Dilated and Hypertrophic CardiomyopathyR24HL117756 · NHLBI · STANFORD UNIVERSITY · PI BUSTAMANTE, CARLOS DANIEL, SNYDER, MICHAEL P. · 2014 to 2018
$8.8M
Induced pluripotent stem cells in the understanding and treatment of heart diseaseU01HL099776 · NHLBI · STANFORD UNIVERSITY · PI LONGAKER, MICHAEL T, WU, JOSEPH C. · 2009 to 2015
$8.2M
Human Induced Pluripotent Stem Cells for Cardiovascular Disease ModelingR01HL113006 · NHLBI · STANFORD UNIVERSITY · PI WU, JOSEPH C. · 2012 to 2025
$6.8M
NHLBI NIH HHS R01 HL113006NHLBI NIH HHS R01HL113006NHLBI NIH HHS R24 HL117756NHLBI NIH HHS R24HL117756NHLBI NIH HHS U01 HL099776NHLBI NIH HHS U01HL099776NIGMS NIH HHS P01 GM099130NIGMS NIH HHS P01GM099130
6 · The paper itself

Abstract

backgroundHuman-induced pluripotent stem cells (iPSCs) are a potentially unlimited source for generation of cardiomyocytes (iPSC-CMs). However, current protocols for iPSC-CM derivation face several challenges, including variability in somatic cell sources and inconsistencies in cardiac differentiation efficiency.

objectivesThis study aimed to assess the effect of epigenetic memory on differentiation and function of iPSC-CMs generated from somatic cell sources of cardiac versus noncardiac origins.

methodsCardiac progenitor cells (CPCs) and skin fibroblasts from the same donors were reprogrammed into iPSCs and differentiated into iPSC-CMs via embryoid body and monolayer-based differentiation protocols.

resultsDifferentiation efficiency was found to be higher in CPC-derived iPSC-CMs (CPC-iPSC-CMs) than in fibroblast-derived iPSC-CMs (Fib-iPSC-CMs). Gene expression analysis during cardiac differentiation demonstrated up-regulation of cardiac transcription factors in CPC-iPSC-CMs, including NKX2-5, MESP1, ISL1, HAND2, MYOCD, MEF2C, and GATA4. Epigenetic assessment revealed higher methylation in the promoter region of NKX2-5 in Fib-iPSC-CMs compared with CPC-iPSC-CMs. Epigenetic differences were found to dissipate with increased cell passaging, and a battery of in vitro assays revealed no significant differences in their morphological and electrophysiological properties at early passage. Finally, cell delivery into a small animal myocardial infarction model indicated that CPC-iPSC-CMs and Fib-iPSC-CMs possess comparable therapeutic capabilities in improving functional recovery in vivo.

conclusionsThis is the first study to compare differentiation of iPSC-CMs from human CPCs versus human fibroblasts from the same donors. The authors demonstrate that although epigenetic memory improves differentiation efficiency of cardiac versus noncardiac somatic cell sources in vitro, it does not contribute to improved functional outcome in vivo.

Indexed as

Stem Cell TransplantationTissue DonorsCell DifferentiationCells, CulturedEmbryonic Stem CellsFibroblastsGene Expression Regulation, DevelopmentalHumansInduced Pluripotent Stem CellsMyocytes, Cardiaccardiac differentiationDNA methylationepigenetic memorypluripotent stem cells

Identifiers

PMID25082575
PMCPMC4134946
OpenAlexW1993554607

What OpenQuestion holds

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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.