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

TitleEnhanced cardiac repair by telomerase reverse transcriptase over-expression in human cardiac mesenchymal stromal cells
Authors
Issue Date2019
PublisherNature Research (part of Springer Nature): Fully open access journals. The Journal's web site is located at http://www.nature.com/srep/index.html
Citation
Scientific Reports, 2019, v. 9 n. 1, p. article no. 10579 How to Cite?
AbstractWe 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.
Persistent Identifierhttp://hdl.handle.net/10722/272726
ISSN
2017 Impact Factor: 4.122
2015 SCImago Journal Rankings: 2.073

 

DC FieldValueLanguage
dc.contributor.authorLe, TYL-
dc.contributor.authorPickett, HA-
dc.contributor.authorYang, A-
dc.contributor.authorHo, JWK-
dc.contributor.authorThavapalachandran, S-
dc.contributor.authorIgoor, S-
dc.contributor.authorYang, SF-
dc.contributor.authorFarraha, M-
dc.contributor.authorVoges, HK-
dc.contributor.authorHudson, JE-
dc.contributor.authordos Remedios, CG-
dc.contributor.authorBryan, TM-
dc.contributor.authorKizana, E-
dc.contributor.authorChong, JJH-
dc.date.accessioned2019-08-06T09:15:25Z-
dc.date.available2019-08-06T09:15:25Z-
dc.date.issued2019-
dc.identifier.citationScientific Reports, 2019, v. 9 n. 1, p. article no. 10579-
dc.identifier.issn2045-2322-
dc.identifier.urihttp://hdl.handle.net/10722/272726-
dc.description.abstractWe 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.-
dc.languageeng-
dc.publisherNature Research (part of Springer Nature): Fully open access journals. The Journal's web site is located at http://www.nature.com/srep/index.html-
dc.relation.ispartofScientific Reports-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleEnhanced cardiac repair by telomerase reverse transcriptase over-expression in human cardiac mesenchymal stromal cells-
dc.typeArticle-
dc.identifier.emailHo, JWK: jwkho@hku.hk-
dc.identifier.authorityHo, JWK=rp02436-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1038/s41598-019-47022-w-
dc.identifier.scopuseid_2-s2.0-85070323605-
dc.identifier.hkuros300265-
dc.identifier.volume9-
dc.identifier.issue1-
dc.identifier.spagearticle no. 10579-
dc.identifier.epagearticle no. 10579-
dc.publisher.placeUnited Kingdom-

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