gms | German Medical Science

27th German Cancer Congress Berlin 2006

German Cancer Society (Frankfurt/M.)

22. - 26.03.2006, Berlin

Tie2/tk transfected Mesenchymal Stem Cells for a combined Stem Cell/Suicide Gene Therapy of Pancreatic Carcinoma

Meeting Abstract

  • corresponding author presenting/speaker Claudius Conrad - Department of Surgery, Klinikum Grosshadern, University of Munich, Deutschland
  • Christiane Bruns - Department of Surgery, Klinikum Grosshadern, University of Munich
  • Hanno Niess - Department of Surgery, Klinikum Grosshadern, University of Munich
  • Ralf Huss - Department of Pathology, University of Munich,
  • Irene von Teichert-Lüttichau - Childrens Hospital, Schwabinger Krankenhaus, Munich
  • Anke Mojaat - Policlinic, Klinikum Innenstadt, University of Munich
  • Karl-Walter Jauch - Department of Surgery, Klinikum Grosshadern, University of Munich
  • Peter Nelson - Policlinic, Klinikum Innenstadt, University of Munich

27. Deutscher Krebskongress. Berlin, 22.-26.03.2006. Düsseldorf, Köln: German Medical Science; 2006. DocOP440

The electronic version of this article is the complete one and can be found online at:

Published: March 20, 2006

© 2006 Conrad et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.



Stem cells and endothelial progenitor cells play an important role in modulating tumour growth. It was our intent to evaluate the role of mesenchymal stem cells (MSC) in the process of tumor angiogenesis and to use them as a vehicle for a suicide construct in a pancreatic tumour model. MSC were obtained from the bone marrow of C57/Bl6-p53 knock out mice. MSCs have been transfected using non-retroviral gene transfer of herpes-simplex-virus-thymidinkinase (tk) under the control of the Tie2 promoter and red fluorescent protein (RFP). Tk leads to phosphorylation of ganciclovir (GCV), which subsequently leads to cell death in the transfected cells and the nearby cell via a bystander effect. Migration assay was performed using a modified Boyden chamber where stem cell migrated against descending concentrations of supernatants from Pan02 syngenic pancreatic carcinoma cells. For in vivo experiments we used an orthotopic pancreatic carcinoma model in C57Bl/6 mice. RFP and tk transfected stem cells were given systemically via i.v. injections. After 28 days tumour size was measured and frozen sections were obtained after the animals had been sacrificed. We were able to demonstrate that there is active migration of MSCs towards supernatants of murine pancreatic carcinoma cells suggesting an active homing mechanism. Moreover, we showed with the orthotopic pancreatic tumour model that non-therapeutic stem cells promote tumour growth were as therapeutic stem cells administered together with GCV led to a reduction of tumour size and peritoneal carcinosis about 50%. Using fluorescent microscopy we were able to find tissue specific expression of RPF of MSCs within the tumour. In summary our data demonstrates active homing of MSC in syngeneic pancreatic cancer leading to enhanced tumor growth. However, this active homing capacity can be used to transport a suicide construct in the tumour. After the tissue specific differentiation of MSCs the Tie2 receptor is activated by Ang-1 leading to expression of thymidinkinase. The enzyme phosphorylates GCV, which leads to cells death of the integrated stem cells as well as cell death of the tumour itself via the so called bystander effect. The reduction in tumour size and the reduced peritoneal carcinosis are promising for the clinical application of a combined stem cell/suicide gene therapy. The selective homing of stem cells in the tumour and the potential use of the patients’ own stem cells indicates little side effects in patients.