| Utility of telomerase-pot1 fusion protein in vascular tissue engineering. | |
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MedLine Citation:
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PMID: 19878625 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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While advances in regenerative medicine and vascular tissue engineering have been substantial in recent years, important stumbling blocks remain. In particular, the limited life span of differentiated cells that are harvested from elderly human donors is an important limitation in many areas of regenerative medicine. Recently, a mutant of the human telomerase reverse transcriptase enzyme (TERT) was described, which is highly processive and elongates telomeres more rapidly than conventional telomerase. This mutant, called pot1-TERT, is a chimeric fusion between the DNA binding protein pot1 and TERT. Because pot1-TERT is highly processive, it is possible that transient delivery of this transgene to cells that are utilized in regenerative medicine applications may elongate telomeres and extend cellular life span while avoiding risks that are associated with retroviral or lentiviral vectors. In the present study, adenoviral delivery of pot1-TERT resulted in transient reconstitution of telomerase activity in human smooth muscle cells, as demonstrated by telomeric repeat amplification protocol (TRAP). In addition, human engineered vessels that were cultured using pot1-TERT-expressing cells had greater collagen content and somewhat better performance in vivo than control grafts. Hence, transient delivery of pot1-TERT to elderly human cells may be useful for increasing cellular life span and improving the functional characteristics of resultant tissue-engineered constructs. |
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Authors:
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Thomas H Petersen; Thomas Hitchcock; Akihito Muto; Elizabeth A Calle; Liping Zhao; Zhaodi Gong; Liqiong Gui; Alan Dardik; Dawn E Bowles; Christopher M Counter; Laura E Niklason |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2009-10-29 |
Journal Detail:
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Title: Cell transplantation Volume: 19 ISSN: 1555-3892 ISO Abbreviation: Cell Transplant Publication Date: 2010 |
Date Detail:
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Created Date: 2010-04-07 Completed Date: 2010-06-29 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 9208854 Medline TA: Cell Transplant Country: United States |
Other Details:
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Languages: eng Pagination: 79-87 Citation Subset: IM |
Affiliation:
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Department of Biomedical Engineering, Duke University, Durham, NC, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adenoviridae
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genetics Adult Animals Bioreactors / standards Blood Vessels / cytology, transplantation* Cell Aging / genetics Cell Culture Techniques Cells, Cultured Collagen / metabolism Genetic Vectors / therapeutic use Graft Survival / genetics Humans Male Muscle, Smooth, Vascular / cytology, metabolism, transplantation Rats Rats, Nude Recombinant Fusion Proteins / genetics, therapeutic use* Telomerase / genetics, therapeutic use* Telomere-Binding Proteins / genetics, therapeutic use* Tissue Engineering / methods* Transfection / methods* |
| Grant Support | |
ID/Acronym/Agency:
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R01 HL083895/HL/NHLBI NIH HHS; R01 HL083895-03/HL/NHLBI NIH HHS; R01 HL083895-04/HL/NHLBI NIH HHS; R21 HL08156/HL/NHLBI NIH HHS; R21 HL081560-01/HL/NHLBI NIH HHS; R21 HL081560-02/HL/NHLBI NIH HHS; T32 GM007171/GM/NIGMS NIH HHS; T32 GM007171-34/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/POT1 protein, human; 0/Recombinant Fusion Proteins; 0/Telomere-Binding Proteins; 9007-34-5/Collagen; EC 2.7.7.49/Telomerase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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