| Controllable expansion of primary cardiomyocytes by reversible immortalization. | |
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MedLine Citation:
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PMID: 19708763 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cardiac tissue engineering will remain only a prospect unless large numbers of therapeutic cells can be provided, either from small samples of cardiac cells or from stem cell sources. In contrast to most adult cells, cardiomyocytes are terminally differentiated and cannot be expanded in culture. We explored the feasibility of enabling the in vitro expansion of primary neonatal rat cardiomyocytes by lentivector-mediated cell immortalization, and then reverting the phenotype of the expanded cells back to the cardiomyocyte state. Primary rat cardiomyocytes were transduced with simian virus 40 large T antigen (TAg), or with Bmi-1 followed by the human telomerase reverse transcriptase (hTERT) gene; the cells were expanded; and the transduced genes were removed by adenoviral vector expressing Cre recombinase. The TAg gene was more efficient in cell transduction than the Bmi-1/hTERT gene, based on the rate of cell proliferation. Immortalized cells exhibited the morphological features of dedifferentiation (increased vimentin expression, and reduced expression of troponin I and Nkx2.5) along with the continued expression of cardiac markers (alpha-actin, connexin-43, and calcium transients). After the immortalization was reversed, cells returned to their differentiated state. This strategy for controlled expansion of primary cardiomyocytes by gene transfer has potential for providing large amounts of a patient's own cardiomyocytes for cell therapy, and the cardiomyocytes derived by this method could be a useful cellular model by which to study cardiogenesis. |
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Authors:
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Yue Zhang; Edem Nuglozeh; Fatouma Touré; Ann Marie Schmidt; Gordana Vunjak-Novakovic |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Human gene therapy Volume: 20 ISSN: 1557-7422 ISO Abbreviation: Hum. Gene Ther. Publication Date: 2009 Dec |
Date Detail:
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Created Date: 2009-12-16 Completed Date: 2010-02-01 Revised Date: 2011-03-03 |
Medline Journal Info:
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Nlm Unique ID: 9008950 Medline TA: Hum Gene Ther Country: United States |
Other Details:
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Languages: eng Pagination: 1687-96 Citation Subset: IM |
Affiliation:
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Department of Biomedical Engineering, Columbia University, New York, NY 10027, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Actins
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biosynthesis Animals Antigens, Polyomavirus Transforming / genetics Cell Differentiation Cell Line, Transformed Connexin 43 / biosynthesis HIV / genetics Homeodomain Proteins / biosynthesis Humans Integrases / genetics Myocytes, Cardiac / metabolism, physiology*, transplantation Nuclear Proteins / genetics Phenotype Proto-Oncogene Proteins / genetics Rats Repressor Proteins / genetics Telomerase / genetics Tissue Engineering / methods* Transcription Factors / biosynthesis Transduction, Genetic Troponin / biosynthesis |
| Grant Support | |
ID/Acronym/Agency:
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R01 HL076485/HL/NHLBI NIH HHS; R01 HL076485-05/HL/NHLBI NIH HHS; R21 HL089913/HL/NHLBI NIH HHS; R21 HL089913-01A1/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Actins; 0/Antigens, Polyomavirus Transforming; 0/Connexin 43; 0/Homeodomain Proteins; 0/Nkx2.5 protein, rat; 0/Nuclear Proteins; 0/Proto-Oncogene Proteins; 0/Repressor Proteins; 0/Transcription Factors; 0/Troponin; 138791-04-5/BMI1 protein, human; EC 2.7.7.-/Cre recombinase; EC 2.7.7.-/Integrases; EC 2.7.7.49/Telomerase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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