gms | German Medical Science

62nd Annual Meeting of the German Society of Neurosurgery (DGNC)
Joint Meeting with the Polish Society of Neurosurgeons (PNCH)

German Society of Neurosurgery (DGNC)

7 - 11 May 2011, Hamburg

Novel aspects of tumorigenesis after stem cell transplantation into the brain: Co-transplantation and survival of feeder-cells as a potential factor affecting tumor formation

Meeting Abstract

  • M. Molcanyi - Klinik für allgemeine Neurochirurgie, Universität zu Köln, Deutschland
  • P. Riess - IFOM, Universität Witten/Herdecke, Deutschland
  • K. Bentz - Syddansk Universitet, Denmark
  • E. Neugebauer - IFOM, Universität Witten/Herdecke, Deutschland
  • R. Goldbrunner - Klinik für allgemeine Neurochirurgie, Universität zu Köln, Deutschland
  • U. Schäfer - Experimentelle Neurotraumatologie, Medizinische Universität, Graz, Österreich

Deutsche Gesellschaft für Neurochirurgie. Polnische Gesellschaft für Neurochirurgen. 62. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Polnischen Gesellschaft für Neurochirurgen (PNCH). Hamburg, 07.-11.05.2011. Düsseldorf: German Medical Science GMS Publishing House; 2011. DocMO.07.09

DOI: 10.3205/11dgnc046, URN: urn:nbn:de:0183-11dgnc0462

Published: April 28, 2011

© 2011 Molcanyi et al.
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Outline

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Objective: Embryonic stem cells seem to possess great therapeutic potential. However, their highly proliferative characteristics (self-renewal potential) combined with the ability to differentiate into all germinal layers (pluripotency) present a potential threat of teratogenesis. Recently, we have identified a currently unknown phenomenon, which may possibly modulate tumor development.

Methods: GFP-transfected murine embryonic stem cells (feeder-dependent D3 line) were implanted into the ipsi- or contralateral cortex of healthy or injured Sprague-Dawley rats (72 hours post fluid-percussion injury). Animals were sacrificed at day 5, day 14 or week 7 post-implantation. Control animals received either saline solution or corresponding amount of feeder cells turned into resting condition prior to inoculation. Brains were examined by conventional and fluorescent double-labeling immunohistochemistry.

Results: Stem cell transplantation into injured brains led to neural differentiation in the absence of tumor formation. A strong post-traumatic inflammatory response impaired the long-term survival and integration of implanted stem cells. Implantation into healthy brains lacking any preliminary inflammatory potential resulted into tumor formation in 65% of animals within initial 2 weeks post-implantation. Neural differentiation was seen solely at the host-graft-interface. Tumor formation occurred at the center of the graft, where the presence of co-transplanted feeder cells was also detected. Control animals developed no tumors. However, in one animal feeder, cells survived over the two-week period.

Conclusions: The absence of tumors in injured animals was apparently due to an inflammatory reaction scavenging the tumorigenic fraction of the implanted graft. This supposition was supported by the outcome of healthy animals receiving stem cells, which were subject to a significant tumor formation. The number of engrafted cells, differentiation status, implantation site and immunosuppressive effects were previously discussed as possible variables determining tumorigenic outcome. Implantation as well as the presence and interactions of co-transplanted feeder-cells possibly driving the stem cells towards non-neuronal differentiation have not yet been taken into account. For the first time we show the survival of co-transplanted feeder cells in terms of contamination of stem cell grafts, possibly affecting the tumorigenic outcome.