Improved lentiviral transduction of human mesenchymal stem cells for therapeutic intervention in pancreatic cancer

Georgios Kallifatidis, B. M. Beckermann, A. Groth, M. Schubert, A. Apel, A. Khamidjanov, E. Ryschich, T. Wenger, W. Wagner, A. Diehlmann, R. Saffrich, U. Krause, V. Eckstein, J. Mattern, M. Chai, G. Schütz, A. D. Ho, M. M. Gebhard, M. W. Büchler, H. FriessP. Büchler, I. Herr

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Genetic modification of human bone marrow mesenchymal stem cells (MSC) is highly valuable for their exploitation in basic science and therapeutic applications, for example in cancer. We present here a new, fast and easy-to-use method to enrich a functional population of lentiviral (LV)-transduced MSC expressing enhanced green fluorescent protein (eGFP). We replaced the eGFP gene by a fusion gene of puromycin acetyltransferase and eGFP. Upon LV gene transfer and puromycin selection, we quickly obtained a pure transduced MSC population, in which growth, differentiation capacity and migration preferences were not compromised. Furthermore, we are the first to report the migration velocity of MSC among which 30% were moving and velocity of about 15 μm h-1 was not altered by LV transduction. Manipulated MSC underwent senescence one passage earlier than non-transduced cells, suggesting the use for therapeutic intervention in early passage numbers. Upon tail vein application in nude mice, the majority of LV-transduced MSC could be detected in human orthotopic pancreatic tumor xenografts and to a minor extent in mouse liver, kidney and lung. Together, LV transduction of genes to MSC followed by puromycin selection is a powerful tool for basic research and improves the therapeutic prospects of MSC as vehicles in gene therapy.

Original languageEnglish (US)
Pages (from-to)231-240
Number of pages10
JournalCancer Gene Therapy
Volume15
Issue number4
DOIs
StatePublished - Apr 1 2008

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Mesenchymal Stromal Cells
Pancreatic Neoplasms
Puromycin
Therapeutics
Genes
Therapeutic Human Experimentation
Acetyltransferases
Cell Aging
Gene Fusion
Medical Genetics
Therapeutic Uses
Heterografts
Nude Mice
Genetic Therapy
Population
Tail
Veins
Neoplasms
Bone Marrow
Kidney

Keywords

  • Gene transfer
  • Homing
  • Lentiviral transduction
  • Mesenchymal stem cells
  • Migration
  • Velocity

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Cancer Research

Cite this

Improved lentiviral transduction of human mesenchymal stem cells for therapeutic intervention in pancreatic cancer. / Kallifatidis, Georgios; Beckermann, B. M.; Groth, A.; Schubert, M.; Apel, A.; Khamidjanov, A.; Ryschich, E.; Wenger, T.; Wagner, W.; Diehlmann, A.; Saffrich, R.; Krause, U.; Eckstein, V.; Mattern, J.; Chai, M.; Schütz, G.; Ho, A. D.; Gebhard, M. M.; Büchler, M. W.; Friess, H.; Büchler, P.; Herr, I.

In: Cancer Gene Therapy, Vol. 15, No. 4, 01.04.2008, p. 231-240.

Research output: Contribution to journalArticle

Kallifatidis, G, Beckermann, BM, Groth, A, Schubert, M, Apel, A, Khamidjanov, A, Ryschich, E, Wenger, T, Wagner, W, Diehlmann, A, Saffrich, R, Krause, U, Eckstein, V, Mattern, J, Chai, M, Schütz, G, Ho, AD, Gebhard, MM, Büchler, MW, Friess, H, Büchler, P & Herr, I 2008, 'Improved lentiviral transduction of human mesenchymal stem cells for therapeutic intervention in pancreatic cancer', Cancer Gene Therapy, vol. 15, no. 4, pp. 231-240. https://doi.org/10.1038/sj.cgt.7701097
Kallifatidis, Georgios ; Beckermann, B. M. ; Groth, A. ; Schubert, M. ; Apel, A. ; Khamidjanov, A. ; Ryschich, E. ; Wenger, T. ; Wagner, W. ; Diehlmann, A. ; Saffrich, R. ; Krause, U. ; Eckstein, V. ; Mattern, J. ; Chai, M. ; Schütz, G. ; Ho, A. D. ; Gebhard, M. M. ; Büchler, M. W. ; Friess, H. ; Büchler, P. ; Herr, I. / Improved lentiviral transduction of human mesenchymal stem cells for therapeutic intervention in pancreatic cancer. In: Cancer Gene Therapy. 2008 ; Vol. 15, No. 4. pp. 231-240.
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AU - Ho, A. D.

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