Evidence map›Paper›PMID 31332256›Full record

ArticleScientific reports2019

Enhanced cardiac repair by telomerase reverse transcriptase over-expression in human cardiac mesenchymal stromal cells.

Thi Yen Loan Le, Hilda A Pickett, Andrian Yang, Joshua W K Ho, Sujitha Thavapalachandran, Sindhu Igoor, Sile F Yang, Melad Farraha, Holly K Voges, James E Hudson and 4 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
2.1field-weighted citation impact, top 11% 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

6 citing papers in PubMed, 20 citations in OpenAlex.

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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 at 3 institutions in 1 country.

Thi Yen Loan LeCentre for Heart Research, Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW, 2145, Australia.ORCID http://orcid.org/0000-0003-1673-7341
Hilda A PickettTelomere Length Regulation Unit, Children's Medical Research Institute, The University of Sydney, Westmead, NSW, 2145, Australia.
Andrian YangVictor Chang Cardiac Research Institute, and St Vincent's Clinical School, University of New South Wales, Darlinghurst, NSW, 2010, Australia.
Joshua W K HoVictor Chang Cardiac Research Institute, and St Vincent's Clinical School, University of New South Wales, Darlinghurst, NSW, 2010, Australia.ORCID http://orcid.org/0000-0003-2331-7011
Sujitha ThavapalachandranCentre for Heart Research, Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW, 2145, Australia.
Sindhu IgoorCentre for Heart Research, Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW, 2145, Australia.
Sile F YangTelomere Length Regulation Unit, Children's Medical Research Institute, The University of Sydney, Westmead, NSW, 2145, Australia.
Melad FarrahaCentre for Heart Research, Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW, 2145, Australia.ORCID http://orcid.org/0000-0003-0656-2816
Holly K VogesSchool of Biomedical Sciences, University of Queensland, St Lucia, Queensland, 4072, Australia.ORCID http://orcid.org/0000-0001-5315-794X
James E HudsonSchool of Biomedical Sciences, University of Queensland, St Lucia, Queensland, 4072, Australia.
Cristobal G Dos RemediosDepartment of Anatomy and Histology, School of Medical Sciences, Bosch Institute, The University of Sydney, Sydney, NSW, 2006, Australia.
Tracy M BryanCell Biology Unit, Children's Medical Research Institute, The University of Sydney, Westmead, NSW, 2145, Australia.ORCID http://orcid.org/0000-0002-7990-5501
Eddy KizanaCentre for Heart Research, Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW, 2145, Australia.
James J H ChongCentre for Heart Research, Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW, 2145, Australia. james.chong@sydney.edu.au.ORCID http://orcid.org/0000-0002-5201-4856
The University of Sydney · AUThe University of Queensland · AUVictor Chang Cardiac Research Institute · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

We have previously reported a subpopulation of mesenchymal stromal cells (MSCs) within the platelet-derived growth factor receptor-alpha (PDGFRα)/CD90 co-expressing cardiac interstitial and adventitial cell fraction. Here we further characterise PDGFRα/CD90-expressing cardiac MSCs (PDGFRα + cMSCs) and use human telomerase reverse transcriptase (hTERT) over-expression to increase cMSCs ability to repair the heart after induced myocardial infarction. hTERT over-expression in PDGFRα + cardiac MSCs (hTERT + PDGFRα + cMSCs) modulates cell differentiation, proliferation, survival and angiogenesis related genes. In vivo, transplantation of hTERT + PDGFRα + cMSCs in athymic rats significantly increased left ventricular function, reduced scar size, increased angiogenesis and proliferation of both cardiomyocyte and non-myocyte cell fractions four weeks after myocardial infarction. In contrast, transplantation of mutant hTERT + PDGFRα + cMSCs (which generate catalytically-inactive telomerase) failed to replicate this cardiac functional improvement, indicating a telomerase-dependent mechanism. There was no hTERT + PDGFRα + cMSCs engraftment 14 days after transplantation indicating functional improvement occurred by paracrine mechanisms. Mass spectrometry on hTERT + PDGFRα + cMSCs conditioned media showed increased proteins associated with matrix modulation, angiogenesis, cell proliferation/survival/adhesion and innate immunity function. Our study shows that hTERT can activate pro-regenerative signalling within PDGFRα + cMSCs and enhance cardiac repair after myocardial infarction. An increased understanding of hTERT's role in mesenchymal stromal cells from various organs will favourably impact clinical regenerative and anti-cancer therapies.

Indexed as

AnimalsChildHumansMesenchymal Stem CellsMesenchymal Stem Cell TransplantationMiddle AgedMyocardial InfarctionMyocytes, CardiacRatsReceptor, Platelet-Derived Growth Factor alphaTelomeraseReceptor, Platelet-Derived Growth Factor alphaTelomerase

Identifiers

PMID31332256
PMCPMC6646304
OpenAlexW2963873578

What OpenQuestion 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 OpenQuestion graph.