Skip to main content

Advertisement

SpringerLink
Log in

The use of hTERT-immortalized cells in tissue engineering

  • Published:
Cytotechnology Aims and scope Submit manuscript

Abstract

The use of human telomerase reverse transcriptase (hTERT)-immortalized cells in tissue engineering protocols is a potentially important application of telomere biology. Several human cell types have been created that overexpress the hTERT gene with enhanced telomerase activity, extended life span and maintained or even improved functional activities. Furthermore, some studies have employed the telomerized cells in tissue engineering protocols with very good results. However, high telomerase activity allows extensive cell proliferation that may be associated with genomic instability and risk for cell transformation. Thus, safety issues should be studied carefully before using the telomerized tissues in the clinic. Alternatively, the development of conditional or intermittent telomerase activation protocols is needed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

TERT/hTERT:

mouse/human telomerase reverse transcriptase

TR:

mouse telomerase RNA

K5:

keratin 5

SMC:

smooth muscle cells

PD:

population doublings

hESC:

human embryonic stem cells

hASC:

human adult stem cells

hMSC:

human mesenchymal stem cells

SV40:

simian virus 40

HPV16:

human papillomavirus type 16

HSC:

hematopoietic stem cells

PGA:

polyglycolic acid

HA/TCP:

hydroxyapatite/tricalcium phosphate.

References

  • R.C. Allsopp G.B. Morin R. DePinho C.B. Harley I.L. Weissman (2003a) ArticleTitleTelomerase is required to slow telomere shortening and extend replicative lifespan of HSCs during serial transplantation Blood 102 517–520 Occurrence Handle10.1182/blood-2002-07-2334

    Article  Google Scholar 

  • R.C. Allsopp G.B. Morin J.W. Horner R. DePinho C.B. Harley I.L. Weissman (2003b) ArticleTitleEffect of TERT over-expression on the long-term transplantation capacity of hematopoietic stem cells Nat. Med. 9 369–371 Occurrence Handle10.1038/nm0403-369

    Article  Google Scholar 

  • R.C. Allsopp I.L. Weissman (2002) ArticleTitleReplicative senescence of hematopoietic stem cells during serial transplantation: does telomere shortening play a role? Oncogene 21 3270–3273 Occurrence Handle10.1038/sj.onc.1205314 Occurrence Handle12032768

    Article  PubMed  Google Scholar 

  • S.E. Artandi S. Alson M.K. Tietze N.E. Sharpless S. Ye R.A. Greenberg D.H. Castrillon J.W. Horner S.R. Weiler R.D. Carrasco R.A. DePinho (2002) ArticleTitleConstitutive telomerase expression promotes mammary carcinomas in aging mice Proc. Natl. Acad. Sci. USA 99 8191–8196 Occurrence Handle10.1073/pnas.112515399 Occurrence Handle12034875

    Article  PubMed  Google Scholar 

  • P. Bianco P.G. Robey (2001) ArticleTitleStem cells in tissue engineering Nature 414 118–121 Occurrence Handle10.1038/35102181 Occurrence Handle11689957

    Article  PubMed  Google Scholar 

  • A.G. Bodnar M. Ouellette M. Frolkis S.E. Holt C.P. Chiu G.B. Morin C.B. Harley J.W. Shay S. Lichtsteiner W.E. Wright (1998) ArticleTitleExtension of life-span by introduction of telomerase into normal human cells Science 279 349–352 Occurrence Handle9454332

    PubMed  Google Scholar 

  • J. Campisi S.H. Kim C.S. Lim M. Rubio (2001) ArticleTitleCellular senescencecancer and aging: the telomere connection Exp. Gerontol. 36 1619–1637 Occurrence Handle10.1016/S0531-5565(01)00160-7 Occurrence Handle11672984

    Article  PubMed  Google Scholar 

  • S. Chang R.A. DePinho (2002) ArticleTitleTelomerase extracurricular activities Proc. Natl. Acad. Sci. USA 99 12520–12522 Occurrence Handle10.1073/pnas.212514699 Occurrence Handle12271146

    Article  PubMed  Google Scholar 

  • S. Di Donna K. Mamchaoui R.N. Cooper S. Seigneurin-Venin J. Tremblay G.S. Butler-Browne V. Mouly (2003) ArticleTitleTelomerase can extend the proliferative capacity of human myoblasts, but does not lead to their immortalization Mol. Cancer Res. 1 643–653 Occurrence Handle12861050

    PubMed  Google Scholar 

  • W.D. Funk C.K. Wang D.N. Shelton C.B. Harley G.D. Pagon W.K. Hoeffler (2000) ArticleTitleTelomerase expression restores dermal integrity to in vitro-aged fibroblasts in a reconstituted skin model Exp. Cell Res. 258 270–278 Occurrence Handle10.1006/excr.2000.4945 Occurrence Handle10896778

    Article  PubMed  Google Scholar 

  • E. Gonzalez-Suarez E. Samper A. Ramirez J.M. Flores J. Martin-Caballero J.L. Jorcano M.A. Blasco (2001) ArticleTitleIncreased epidermal tumors and increased skin wound healing in transgenic mice overexpressing the catalytic subunit of telomerasemTERT, in basal keratinocytes EMBO J. 20 2619–2630 Occurrence Handle10.1093/emboj/20.11.2619 Occurrence Handle11387197

    Article  PubMed  Google Scholar 

  • S. Gronthos S.Q. Chen C.Y. Wang P.G. Robey S.T. Shi (2003) ArticleTitleTelomerase accelerates osteogenesis of bone marrow stromal stem cells by upregulation of CBFA1, osterix, and osteocalcin J. Bone Miner. Res. 18 716–722 Occurrence Handle12674332

    PubMed  Google Scholar 

  • C.B. Harley (1991) ArticleTitleTelomere loss: mitotic clock or genetic time bomb? Mutat. Res. 256 271–282 Occurrence Handle1722017

    PubMed  Google Scholar 

  • H.S. Huang J.F. Chiou Y. Fong C.C. Hou Y.C. Lu J.Y. Wang J.W. Shih Y.R. Pan J.J. Lin (2003) ArticleTitleActivation of human telomerase reverse transcriptase expression by some new symmetrical bis-substituted derivatives of the anthraquinone J. Med. Chem. 46 3300–3307 Occurrence Handle10.1021/jm020492l Occurrence Handle12852760

    Article  PubMed  Google Scholar 

  • X.R. Jiang G. Jimenez E. Chang M. Frolkis B. Kusler M. Sage M. Beeche A.G. Bodnar G.M. Wahl T.D. Tlsty C.P. Chiu (1999) ArticleTitleTelomerase expression in human somatic cells does not induce changes associated with a transformed phenotype Nat. Genet. 21 111–114 Occurrence Handle10.1038/5056 Occurrence Handle9916802

    Article  PubMed  Google Scholar 

  • Y. Jiang B. Vaessen T. Lenvik M. Blackstad M. Reyes C.M. Verfaillie (2002) ArticleTitleMultipotent progenitor cells can be isolated from postnatal murine bone marrow, muscleand brain Exp. Hematol. 30 896–904 Occurrence Handle10.1016/S0301-472X(02)00869-X Occurrence Handle12160841

    Article  PubMed  Google Scholar 

  • H.J. Kang Y.S. Choi S.B. Hong K.W. Kim R.S. Woo S.J. Won E.J. Kim H.K. Jeon S.Y. Jo T.K. Kim R. Bachoo I.J. Reynolds B.J. Gwag H.W. Lee (2004) ArticleTitleEctopic expression of the catalytic subunit of telomerase protects against brain injury resulting from ischemia and NMDA-induced neurotoxicity J. Neurosci. 24 1280–1287 Occurrence Handle10.1523/JNEUROSCI.4082-03.2004 Occurrence Handle14960598

    Article  PubMed  Google Scholar 

  • M. Kassem L. Ankersen E.F. Eriksen B.F. Clark S.I. Rattan (1997) ArticleTitleDemonstration of cellular aging and senescence in serially passaged long-term cultures of human trabecular osteoblasts Osteopor. Intern. 7 514–524

    Google Scholar 

  • M. Kveiborg S.I. Rattan B.F. Clark E.F. Eriksen M. Kassem (2001) ArticleTitleTreatment with 1,25-dihydroxyvitamin D3 reduces impairment of human osteoblast functions during cellular aging in culture J. Cell Physiol. 186 298–306 Occurrence Handle10.1002/1097-4652(200002)186:2<298::AID-JCP1030>3.0.CO;2-H Occurrence Handle11169466

    Article  PubMed  Google Scholar 

  • L. Liu C.M. DiGirolamo P.A. Navarro M.A. Blasco D.L. Keefe (2004) ArticleTitleTelomerase deficiency impairs differentiation of mesenchymal stem cells Exp. Cell Res. 294 3116–3121 Occurrence Handle10.1016/j.yexcr.2003.10.031

    Article  Google Scholar 

  • J.A. Martin C.J. Mitchell A.J. Klingelhutz J.A. Buckwalter (2002) ArticleTitleEffects of telomerase and viral oncogene expression on the in vitro growth of human chondrocytes J. Gerontol. Ser. A-Biol. Sci. Med. Sci. 57 B48–B53

    Google Scholar 

  • J.A. McKee S.S.R. Banik M.J. Boyer N.M. Hamad J.H. Lawson L.E. Niklason C.M. Counter (2003) ArticleTitleHuman arteries engineered in vitro EMBO Report 4 633–638 Occurrence Handle10.1038/sj.embor.embor847

    Article  Google Scholar 

  • M. Milyavsky I. Shats N. Erez X. Tang S. Senderovich A. Meerson Y. Tabach N. Goldfinger D. Ginsberg C.C. Harris V. Rotter (2003) ArticleTitleProlonged culture of telomerase-immortalized human fibroblasts leads to a premalignant phenotype Cancer Res. 63 7147–7157 Occurrence Handle14612508

    PubMed  Google Scholar 

  • C.P. Morales S.E. Holt M. Ouellette K.J. Kaur Y. Yan K.S. Wilson M.A. White W.E. Wright J.W. Shay (1999) ArticleTitleAbsence of cancer-associated changes in human fibroblasts immortalized with telomerase Nat. Genet. 21 115–118 Occurrence Handle10.1038/5063 Occurrence Handle9916803

    Article  PubMed  Google Scholar 

  • S. Murasawa J. Llevadot M. Silver J.M. Isner D.W. Losordo T. Asahara (2002) ArticleTitleConstitutive human telomerase reverse transcriptase expression enhances regenerative properties of endothelial progenitor cells Circulation 106 1133–1139 Occurrence Handle10.1161/01.CIR.0000027584.85865.B4 Occurrence Handle12196341

    Article  PubMed  Google Scholar 

  • J.R. Noble Z.H. Zhong A.A. Neumann J.R. Melki S.J. Clark R.R. Reddel (2004) ArticleTitleAlterations in the p16(INK4a) and p53 tumor suppressor genes of hTERT-immortalized human fibroblasts Oncogene 23 3116–3121 Occurrence Handle10.1038/sj.onc.1207440 Occurrence Handle14743210

    Article  PubMed  Google Scholar 

  • J.S. Odorico D.S. Kaufman J.A. Thomson (2001) ArticleTitleMultilineage differentiation from human embryonic stem cell lines Stem. Cells 19 193–204 Occurrence Handle10.1634/stemcells.19-3-193 Occurrence Handle11359944

    Article  PubMed  Google Scholar 

  • H. Oh G.E. Taffet K.A. Youker M.L. Entman P.A. Overbeek L.H. Michael M.D. Schneider (2001) ArticleTitleTelomerase reverse transcriptase promotes cardiac muscle cell proliferation, hypertrophy, and survival Proc. Natl. Acad. Sci. USA 98 10308–10313 Occurrence Handle10.1073/pnas.191169098 Occurrence Handle11517337

    Article  PubMed  Google Scholar 

  • L. Rambhatla C.P. Chiu R.D. Glickman C. Rowe-Rendleman (2002) ArticleTitleIn vitro differentiation capacity of telomerase immortalized human RPE cells Invest. Ophthalmol. Vis. Sci. 43 1622–1630 Occurrence Handle11980883

    PubMed  Google Scholar 

  • M.S. Rao M.P. Mattson (2001) ArticleTitleStem cells and aging: expanding the possibilities Mech. Ageing Dev. 122 713–734 Occurrence Handle10.1016/S0047-6374(01)00224-X Occurrence Handle11322994

    Article  PubMed  Google Scholar 

  • S.I.S. Rattan (2003) Aging outside the body: usefulneess of the Hayflick system S.C. Kaul R. Wadhwa (Eds) Aging of Cells in and Outside the Body Kluwer Academic Publishers London 1–8

    Google Scholar 

  • M. Rubio S.H. Kim J. Campisi (2004) ArticleTitleReversible manipulation of telomerase expression and telomere length. Implications for the ionizing radiation response and replicative senescence of human cells J. Biol. Chem. 277 28609–28617 Occurrence Handle10.1074/jbc.M203747200

    Article  Google Scholar 

  • N. Serakinci P. Guldberg J.S. Burns B.M. Abdallah H. Schroedder T. Jensen M. Kassem (2004) ArticleTitleAdult human mesenchymal stem cell as a target for neoplastic transformation Oncogene 23 5095–5098 Occurrence Handle10.1038/sj.onc.1207651 Occurrence Handle15107831

    Article  PubMed  Google Scholar 

  • M.J. Shamblott J. Axelman S.P. Wang E.M. Bugg J.W. Littlefield P.J. Donovan P.D. Blumenthal G.R. Huggins J.D. Gearhart (1998) ArticleTitleDerivation of pluripotent stem cells horn cultured human primordial germ cells Proc. Natl. Acad. Sci. USA 95 13726–13731 Occurrence Handle10.1073/pnas.95.23.13726 Occurrence Handle9811868

    Article  PubMed  Google Scholar 

  • J.W. Shay W.E. Wright (2000a) ArticleTitleHayflick, his limitand cellular ageing Nat. Rev. Mol. Cell Biol. 1 72–76 Occurrence Handle10.1038/35036093

    Article  Google Scholar 

  • J.W. Shay W.E. Wright (2000b) ArticleTitleThe use of telomerized cells for tissue engineering Nat. Biotechnol. 18 22–23 Occurrence Handle10.1038/71872

    Article  Google Scholar 

  • S. Shi S. Gronthos S. Chen A. Reddi C.M. Counter P.G. Robey C.Y. Wang (2002) ArticleTitleBone formation by human postnatal bone marrow stromal stem cells is enhanced by telomerase expression Nat. Biotechnol. 20 587–591 Occurrence Handle10.1038/nbt0602-587 Occurrence Handle12042862

    Article  PubMed  Google Scholar 

  • J.L. Simonsen C. Rosada N. Serakinci J. Justesen K. Stenderup S.I. Rattan T.G. Jensen M. Kassem (2002) ArticleTitleTelomerase expression extends the proliferative life-span and maintains the osteogenic potential of human bone marrow stromal cells Nat. Biotechnol. 20 592–596 Occurrence Handle10.1038/nbt0602-592 Occurrence Handle12042863

    Article  PubMed  Google Scholar 

  • K. Stenderup J. Justesen C. Clausen M. Kassem (2003) ArticleTitleAging is associated with decreased maximal life span and accelerated senescence of bone marrow stromal cells Bone 33 919–926 Occurrence Handle10.1016/j.bone.2003.07.005 Occurrence Handle14678851

    Article  PubMed  Google Scholar 

  • U.A. Stock J.P. Vacanti (2001) ArticleTitleTissue engineering: Current state and prospects Ann. Rev. Med. 52 443–451 Occurrence Handle10.1146/annurev.med.52.1.443 Occurrence Handle11160788

    Article  PubMed  Google Scholar 

  • M. Thomas L.Q. Yang P.J. Hornsby (2000) ArticleTitleFormation of functional tissue from transplanted adrenocortical cells expressing telomerase reverse transcriptase Nat. Biotechnol. 18 39–42 Occurrence Handle10.1038/71894 Occurrence Handle10625388

    Article  PubMed  Google Scholar 

  • M.R. Wada P. Polly A. Nagpal S.C. Kaul (2003) Escaping cellular senescence in vitro SIS Rattan (Eds) Modulating Aging and Longevity Kluwer Academic Publishers London 85–89

    Google Scholar 

  • F.M. Watt B.L. Hogan (2000) ArticleTitleOut of Eden: stem cells and their niches Science 287 1427–1430 Occurrence Handle10.1126/science.287.5457.1427 Occurrence Handle10688781

    Article  PubMed  Google Scholar 

  • H. Wege H.T. Le M.S. Chui L. Liu J. Wu R. Giri H. Malhi B.S. Sappal V. Kumaran S. Gupta M.A. Zern (2003) ArticleTitleTelomerase reconstitution immortalizes human fetal hepatocytes without disrupting their differentiation potential Gastroenterology 124 432–444 Occurrence Handle10.1053/gast.2003.50064 Occurrence Handle12557149

    Article  PubMed  Google Scholar 

  • W.E. Wright J.W. Shay (2002) ArticleTitleHistorical claims and current interpretations of replicative aging Nat. Biotechnol. 20 682–688 Occurrence Handle10.1038/nbt0702-682 Occurrence Handle12089552

    Article  PubMed  Google Scholar 

  • J. Yang U. Nagavarapu K. Relloma M.D. Sjaastad W.C. Moss A. Passaniti G.S. Herron (2001) ArticleTitleTelomerized human microvasculature is functional in vivo Nat. Biotechnol. 19 219–224 Occurrence Handle10.1038/85655 Occurrence Handle11231553

    Article  PubMed  Google Scholar 

  • K. Yudoh K. Nishioka (2004) ArticleTitletelomerized presenescent osteoblasts prevent bone mass loss in vivo Gene therapy 11 909–915 Occurrence Handle10.1038/sj.gt.3302234 Occurrence Handle15057262

    Article  PubMed  Google Scholar 

  • S. Zimmermann M. Voss S. Kaiser U. Kapp C.F. Waller U.M. Martens (2003) ArticleTitleLack of telomerase activity in human mesenchymal stem cells Leukemia 17 1146–1149 Occurrence Handle10.1038/sj.leu.2402962 Occurrence Handle12764382

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Endocrinology and Metabolism, University Hospital of Odense, DK-5000, Odense C, Denmark

    Moustapha Kassem, Basem M. Abdallah, Zentao Yu, Nicholas Ditzel & Jorge S. Burns

Authors
  1. Moustapha Kassem
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Basem M. Abdallah
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zentao Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nicholas Ditzel
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jorge S. Burns
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Moustapha Kassem.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kassem, M., Abdallah, B.M., Yu, Z. et al. The use of hTERT-immortalized cells in tissue engineering. Cytotechnology 45, 39–46 (2004). https://doi.org/10.1007/s10616-004-5124-2

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10616-004-5124-2

Keywords

Search

Navigation