gms | German Medical Science

61st Annual Meeting of the German Society of Neurosurgery (DGNC) as part of the Neurowoche 2010
Joint Meeting with the Brazilian Society of Neurosurgery on the 20 September 2010

German Society of Neurosurgery (DGNC)

21 - 25 September 2010, Mannheim

Non-invasive intranasal application of neural stem cells to target intracerebral glioblastoma

Meeting Abstract

  • Matthias Reitz - Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Hamburg-Eppendorf, Deutschland
  • Maria Demestre - Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Hamburg-Eppendorf, Deutschland
  • Hildegard Meissner - Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Hamburg-Eppendorf, Deutschland
  • Katrin Lamszus - Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Hamburg-Eppendorf, Deutschland
  • Manfred Westphal - Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Hamburg-Eppendorf, Deutschland
  • Nils Ole Schmidt - Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Hamburg-Eppendorf, Deutschland

Deutsche Gesellschaft für Neurochirurgie. 61. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC) im Rahmen der Neurowoche 2010. Mannheim, 21.-25.09.2010. Düsseldorf: German Medical Science GMS Publishing House; 2010. DocV1542

DOI: 10.3205/10dgnc019, URN: urn:nbn:de:0183-10dgnc0194

Published: September 16, 2010

© 2010 Reitz 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: Neural stem cells (NSC) display inherent tumor-tropic properties that can be exploited for targeted delivery of therapeutic genes to invasive glioma cells. Optimized transplantation efficiency is essential for developing effective NSC-based glioma therapies. Current strategies aim to deliver genetically-modified NSC by direct intracerebral or intracavitary application immediately after glioma resection. However, from clinical experience in other neurological disorders it is well known that effective intracerebral delivery of cells is hampered by an extremely low transplantation efficiency when injected directly into the brain parenchyma. Recently, intranasal delivery has been demonstrated as a noninvasive and convenient method to rapidly deliver drugs to the CNS, bypassing the blood-brain-barrier and minimizing systemic exposure.

Methods: In order to determine the feasibility of intranasally applied neural stem cells to target intracerebrally growing brain tumors we used the orthotopic U87 and G55 human glioblastoma models in nude mice (n=10). A cell suspension of 3x105 eGFP-expressing murine neural stem cells/mouse were applied as nose drops to the nostrils. Seven days after intranasal application the brain and internal organs were harvested and immunohistological analyses were performed to assess the distribution and tumor tropism of eGFP-positive NSC.

Results: Seven days after intranasal delivery of NSC we found the vast majority of GFP-positive cells closely surrounding the intracerebrally growing glioma xenografts and enriching within the tumor mass. Even small satellite tumors distant from the main tumor mass were targeted by NSC. Quantification revealed up to 421 NSC/mm2 within the tumors and up to 907 NSC/mm2 in the immediate tumor/brain parenchyma border zone. Some GFP-positive cells were found in the olfactory bulb and in deeper brain structures suggesting that the olfactory and trigeminal pathways were utilized to enter the intracerebral compartment.

Conclusions: Here, we demonstrate proof-of-concept that the non-invasive intranasal application of neural stem cells as nose drops allows highly motile NSC to enter the brain and displays a targeted migration of NSC towards intracerebral glioma. Our data suggests that the intranasal application of cells has the potential to serve as a simple and non-invasive alternative delivery method during a complex intracerebrebral disease process.