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Utility of telomerase-pot1 fusion protein in vascular tissue engineering.
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.
Type
Journal articleSubject
AdenoviridaeAdult
Animals
Bioreactors
Blood Vessels
Cell Aging
Cell Culture Techniques
Cells, Cultured
Collagen
Genetic Vectors
Graft Survival
Humans
Male
Muscle, Smooth, Vascular
Rats
Rats, Nude
Recombinant Fusion Proteins
Telomerase
Telomere-Binding Proteins
Tissue Engineering
Transfection
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https://hdl.handle.net/10161/4616Published Version (Please cite this version)
10.3727/096368909X478650Publication Info
Petersen, Thomas H; Hitchcock, Thomas; Muto, Akihito; Calle, Elizabeth A; Zhao, Liping;
Gong, Zhaodi; ... Niklason, Laura E (2010). Utility of telomerase-pot1 fusion protein in vascular tissue engineering. Cell Transplant, 19(1). pp. 79-87. 10.3727/096368909X478650. Retrieved from https://hdl.handle.net/10161/4616.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Christopher M. Counter
George Barth Geller Distinguished Professor of Pharmacology
The Counter lab studies the molecular mechanisms that underly to the onset of human
cancers, with the goal to prevent cancer initiation or progression. The lab uses
ultra-senstitive sequencing platforms and proteomic-coupled CRISPR/Cas9 screens to
elucidate the factors that mold the mutational patterns selected to initiate the process
of tumorigenesis. See https://counter.labs.duke.edu/ for further details.

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