Publication:
Nucleus pulposus cellular longevity by telomerase gene therapy

dc.contributor.author Chung, Sylvia en_US
dc.contributor.author Wei, Ai-Qun en_US
dc.contributor.author Connor, David en_US
dc.contributor.author Webb, Graham en_US
dc.contributor.author Molloy, Tim en_US
dc.contributor.author Pajic, Marina en_US
dc.contributor.author Diwan, Ashish en_US
dc.date.accessioned 2021-11-25T15:30:10Z
dc.date.available 2021-11-25T15:30:10Z
dc.date.issued 2007 en_US
dc.description.abstract Study Design. Nonviral transfection of nucleus pulposus cells with a telomerase expression construct to assess the effects on cellular lifespan, function, karyotypic stability, and transformation properties. Objectives. To investigate whether telomerase gene therapy can extend the cellular lifespan while retaining functionality of nucleus pulposus cells in a safe manner. Summary of Background Data. Degeneration of the intervertebral disc is an age-related condition in which cells responsible for the maintenance and health of the disc deteriorate with age. Telomerase can extend the cellular lifespan and function of other musculoskeletal tissues, such as the heart, bones, and connective tissues. Therefore, extension of the cellular lifespan and matrix production of intervertebral disc cells may have the potential to delay the degeneration process. Methods. Ovine nucleus pulposus cells were lipofectamine transfected in vitro with a human telomerase reverse transcriptase (hTERT) expression construct. Cellular lifespan and matrix transcript levels were determined by cumulative population doublings and real-time RT-PCR, respectively. G1-cell cycle checkpoint, p53 functionality, growth of transfected cells in anchorage-independent or serum starvation conditions, and karyotypic analysis were performed. Results. Transfection was achieved successfully with 340% +/- 7% ( mean +/- SD) relative telomerase activity in hTERT- transfected cells. hTERT transfection enabled a 50% extension in mean cellular lifespan and prolonged matrix production of collagen 1 and 2 for more than 282 days. Karyotypic instability was detected but G1-cell cycle checkpoint and p53 was functionally comparable to parental cells with no growth in serum starvation or anchorage-independent conditions. Conclusions. Telomerase can extend the cellular lifespan of nucleus pulposus cells and prolong the production of extracellular matrix. Safety is still unresolved, as karyotypic instability was detected but no l en_US
dc.identifier.issn 0362-2436 en_US
dc.identifier.uri http://hdl.handle.net/1959.4/44645
dc.language English
dc.language.iso EN en_US
dc.rights CC BY-NC-ND 3.0 en_US
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/3.0/au/ en_US
dc.source Legacy MARC en_US
dc.subject.other telomerase en_US
dc.subject.other nonviral transfection en_US
dc.subject.other nucleus pulposus cells en_US
dc.subject.other gene en_US
dc.subject.other therapy en_US
dc.subject.other real-time RT-PCR en_US
dc.subject.other telomere length-independent en_US
dc.subject.other life extension en_US
dc.title Nucleus pulposus cellular longevity by telomerase gene therapy en_US
dc.type Journal Article en
dcterms.accessRights metadata only access
dspace.entity.type Publication en_US
unsw.accessRights.uri http://purl.org/coar/access_right/c_14cb
unsw.identifier.doiPublisher http://dx.doi.org/10.1097/BRS.0b013e31805471a3 en_US
unsw.relation.faculty Medicine & Health
unsw.relation.ispartofissue 11 en_US
unsw.relation.ispartofjournal Spine en_US
unsw.relation.ispartofpagefrompageto 1188-1196 en_US
unsw.relation.ispartofvolume 32 en_US
unsw.relation.originalPublicationAffiliation Chung, Sylvia, Clinical School - St George Hospital, Faculty of Medicine, UNSW en_US
unsw.relation.originalPublicationAffiliation Wei, Ai-Qun, Clinical School - St George Hospital, Faculty of Medicine, UNSW en_US
unsw.relation.originalPublicationAffiliation Connor, David, Clinical School - St Vincent's Hospital, Faculty of Medicine, UNSW en_US
unsw.relation.originalPublicationAffiliation Webb, Graham en_US
unsw.relation.originalPublicationAffiliation Molloy, Tim, Clinical School - St George Hospital, Faculty of Medicine, UNSW en_US
unsw.relation.originalPublicationAffiliation Pajic, Marina, Children's Cancer Institute Australia for Medical Research, Faculty of Medicine, UNSW en_US
unsw.relation.originalPublicationAffiliation Diwan, Ashish, Clinical School - St George Hospital, Faculty of Medicine, UNSW en_US
unsw.relation.school Clinical School St George Hospital *
unsw.relation.school Clinical School St Vincents Hospital *
unsw.relation.school Childhood Cancer Research *
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