دورية أكاديمية
أعرض في EDS

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

التفاصيل البيبلوغرافية
العنوان: Enhanced cardiac repair by telomerase reverse transcriptase over-expression in human cardiac mesenchymal stromal cells.
المؤلفون: Le TYL; Centre for Heart Research, Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW, 2145, Australia.; Department of Cardiology, Westmead Hospital, Westmead, NSW, 2145, Australia., Pickett HA; Telomere Length Regulation Unit, Children's Medical Research Institute, The University of Sydney, Westmead, NSW, 2145, Australia., Yang A; Victor Chang Cardiac Research Institute, and St Vincent's Clinical School, University of New South Wales, Darlinghurst, NSW, 2010, Australia., Ho JWK; Victor Chang Cardiac Research Institute, and St Vincent's Clinical School, University of New South Wales, Darlinghurst, NSW, 2010, Australia., Thavapalachandran S; Centre for Heart Research, Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW, 2145, Australia.; Department of Cardiology, Westmead Hospital, Westmead, NSW, 2145, Australia.; Sydney Medical School, The University of Sydney, Sydney, NSW, 2006, Australia., Igoor S; Centre for Heart Research, Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW, 2145, Australia.; Department of Cardiology, Westmead Hospital, Westmead, NSW, 2145, Australia., Yang SF; Telomere Length Regulation Unit, Children's Medical Research Institute, The University of Sydney, Westmead, NSW, 2145, Australia., Farraha M; Centre for Heart Research, Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW, 2145, Australia.; Department of Cardiology, Westmead Hospital, Westmead, NSW, 2145, Australia.; Sydney Medical School, The University of Sydney, Sydney, NSW, 2006, Australia., Voges HK; School of Biomedical Sciences, University of Queensland, St Lucia, Queensland, 4072, Australia., Hudson JE; School of Biomedical Sciences, University of Queensland, St Lucia, Queensland, 4072, Australia., Dos Remedios CG; Department of Anatomy and Histology, School of Medical Sciences, Bosch Institute, The University of Sydney, Sydney, NSW, 2006, Australia., Bryan TM; Cell Biology Unit, Children's Medical Research Institute, The University of Sydney, Westmead, NSW, 2145, Australia., Kizana E; Centre for Heart Research, Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW, 2145, Australia.; Department of Cardiology, Westmead Hospital, Westmead, NSW, 2145, Australia.; Sydney Medical School, The University of Sydney, Sydney, NSW, 2006, Australia., Chong JJH; Centre for Heart Research, Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW, 2145, Australia. james.chong@sydney.edu.au.; Department of Cardiology, Westmead Hospital, Westmead, NSW, 2145, Australia. james.chong@sydney.edu.au.; Sydney Medical School, The University of Sydney, Sydney, NSW, 2006, Australia. james.chong@sydney.edu.au.; Victor Chang Cardiac Research Institute, Darlinghurst, NSW, 2010, Australia. james.chong@sydney.edu.au.
المصدر: Scientific reports [Sci Rep] 2019 Jul 22; Vol. 9 (1), pp. 10579. Date of Electronic Publication: 2019 Jul 22.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : Nature Publishing Group, copyright 2011-
مواضيع طبية MeSH: Mesenchymal Stem Cell Transplantation/*methods , Mesenchymal Stem Cells/*enzymology , Myocardial Infarction/*therapy , Myocytes, Cardiac/*enzymology , Telomerase/*metabolism, Animals ; Child ; Humans ; Middle Aged ; Myocytes, Cardiac/transplantation ; Rats ; Receptor, Platelet-Derived Growth Factor alpha/metabolism
مستخلص: 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.
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المشرفين على المادة: EC 2.7.10.1 (Receptor, Platelet-Derived Growth Factor alpha)
EC 2.7.7.49 (Telomerase)
تواريخ الأحداث: Date Created: 20190724 Date Completed: 20201026 Latest Revision: 20210110
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC6646304
DOI: 10.1038/s41598-019-47022-w
PMID: 31332256
قاعدة البيانات: MEDLINE
الوصف
تدمد:2045-2322
DOI:10.1038/s41598-019-47022-w