Utility of telomerase-pot1 fusion protein in vascular tissue engineering.

dc.contributor.author

Petersen, Thomas H

dc.contributor.author

Hitchcock, Thomas

dc.contributor.author

Muto, Akihito

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Calle, Elizabeth A

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Zhao, Liping

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Gong, Zhaodi

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Gui, Liqiong

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Dardik, Alan

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Bowles, Dawn E

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Counter, Christopher M

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Niklason, Laura E

dc.coverage.spatial

United States

dc.date.accessioned

2011-06-21T17:32:24Z

dc.date.issued

2010

dc.description.abstract

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.

dc.description.version

Version of Record

dc.identifier

https://www.ncbi.nlm.nih.gov/pubmed/19878625

dc.identifier

ct2075petersen

dc.identifier.eissn

1555-3892

dc.identifier.uri

https://hdl.handle.net/10161/4616

dc.language

eng

dc.language.iso

en_US

dc.publisher

SAGE Publications

dc.relation.ispartof

Cell Transplant

dc.relation.isversionof

10.3727/096368909X478650

dc.relation.journal

Cell transplantation

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Adenoviridae

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Adult

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Animals

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Bioreactors

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Blood Vessels

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Cell Aging

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Cell Culture Techniques

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Cells, Cultured

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Collagen

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Genetic Vectors

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Graft Survival

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Humans

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Male

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Muscle, Smooth, Vascular

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Rats

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Rats, Nude

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Recombinant Fusion Proteins

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Telomerase

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Telomere-Binding Proteins

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Tissue Engineering

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Transfection

dc.title

Utility of telomerase-pot1 fusion protein in vascular tissue engineering.

dc.title.alternative
dc.type

Journal article

duke.contributor.orcid

Counter, Christopher M|0000-0003-0748-3079

duke.date.pubdate

2010-00-00

duke.description.issue

1

duke.description.volume

19

pubs.author-url

https://www.ncbi.nlm.nih.gov/pubmed/19878625

pubs.begin-page

79

pubs.end-page

87

pubs.issue

1

pubs.organisational-group

Basic Science Departments

pubs.organisational-group

Clinical Science Departments

pubs.organisational-group

Duke

pubs.organisational-group

Duke Cancer Institute

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Institutes and Centers

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Pharmacology & Cancer Biology

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Radiation Oncology

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School of Medicine

pubs.organisational-group

Surgery

pubs.organisational-group

Surgery, Surgical Sciences

pubs.publication-status

Published

pubs.volume

19

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