gms | German Medical Science

57th Annual Meeting of the German Society of Neurosurgery
Joint Meeting with the Japanese Neurosurgical Society

German Society of Neurosurgery (DGNC)

11 - 14 May, Essen

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Distinct distribution patterns of adult mesenchymal stem cells in tumor bearing brain after local and systemic application

Verteilungsmuster adulter mesenchymaler Stammzellen im Glioblastom-infiltrierten Gehirn nach lokaler und systemischer Gabe

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  • corresponding author C. Schichor - Department of Neurosurgery, Ludwig-Maximilians-Universität München
  • F. Trillsch - Department of Neurosurgery, Ludwig-Maximilians-Universität München
  • S. Loos - Department of Neurosurgery, Ludwig-Maximilians-Universität München
  • B. Krebs - Dept. Neuropathology, Ludwig-Maximilians-Universität München
  • P. Nelson - Med. Poliklinik, Ludwig-Maximilians-Universität München
  • R. Goldbrunner - Department of Neurosurgery, Ludwig-Maximilians-Universität München

Deutsche Gesellschaft für Neurochirurgie. Japanische Gesellschaft für Neurochirurgie. 57. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), Joint Meeting mit der Japanischen Gesellschaft für Neurochirurgie. Essen, 11.-14.05.2006. Düsseldorf, Köln: German Medical Science; 2006. DocSO.03.04

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/dgnc2006/06dgnc176.shtml

Published: May 8, 2006

© 2006 Schichor et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

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Objective: Much effort has been put into establishing human mesenchymal stem cells (hMSC) as carriers for malignant glioma therapy. Aim of our current study was to assess intracerebral distribution patterns of MSC that have been applied locally versus systemic injection of MSC with a special regard on integration of MSC into the vasculature.

Methods: Human MSC were isolated from bone marrow biopsies carried out for haematological indications. U373-GFP gliomas were generated by orthotopic implantation into T-cell deficient rats. DiI stained hMSC were injected 3 mm distant from the gliomas and the migration of these cells assessed by confocal microscopy. Incisions without glioma inoculation, immobilized MSC and fibroblasts served as controls. In a second setting, a murine MSC cell line (mMSC) was transfected with a RFP/Tie-2-promotor gene and applied intravenously in glioma bearing rats. Tie2 induced expression of RFP allowed fluorescence microscopic detection of those mMSC, which integrated into the endothelial lining of the tumor vasculature. Immunohistochemically, transfected MSC were detected by anti-SV40 staining.

Results: After local application, a high degree of colocalization of hMSC and the solid tumor as well as infiltrating tumor cells was observed. Passive translocalization of MSC as well as tropism to the pure incision could be excluded by the controls. Intravenously administered mMSC showed extensive tropism to the glioma. Especially, the infiltrating borders of the tumor showed accumulation of hMSC. Strong RFP expression could detect an integration of mMSC into the vasculature of the glioma. This phenomenon was confirmed immunohistochemically by anti-SV40 staining.

Conclusions: Since hMSC show intensive tropism to solid gliomas and invading glioma cells they can be regarded as potential vectors for a general anti glioma therapy. The novel observation of an integration of murine MSC into tumor vessels has to be further evaluated for reproducibility in human MSC and for the risk potential in case of therapeutic application.