gms | German Medical Science

63rd Annual Meeting of the German Society of Neurosurgery (DGNC)
Joint Meeting with the Japanese Neurosurgical Society (JNS)

German Society of Neurosurgery (DGNC)

13 - 16 June 2012, Leipzig

Intranasal administration: A non-invasive, direct passage for the delivery of glioma-targeting neural stem/progenitor cells

Meeting Abstract

  • M. Reitz - Neurochirurgische Klinik, Universitäts-Krankenhaus Eppendorf, Hamburg
  • M. Demestre - Neurochirurgische Klinik, Universitäts-Krankenhaus Eppendorf, Hamburg
  • J. Sedlacik - Universitäts-Krankenhaus Eppendorf, Hamburg
  • H. Meissner - Neurochirurgische Klinik, Universitäts-Krankenhaus Eppendorf, Hamburg
  • M. Westphal - Neurochirurgische Klinik, Universitäts-Krankenhaus Eppendorf, Hamburg
  • N.O. Schmidt - Neurochirurgische Klinik, Universitäts-Krankenhaus Eppendorf, Hamburg

Deutsche Gesellschaft für Neurochirurgie. Japanische Gesellschaft für Neurochirurgie. 63. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Japanischen Gesellschaft für Neurochirurgie (JNS). Leipzig, 13.-16.06.2012. Düsseldorf: German Medical Science GMS Publishing House; 2012. DocSA.01.04

DOI: 10.3205/12dgnc302, URN: urn:nbn:de:0183-12dgnc3029

Published: June 4, 2012

© 2012 Reitz et al.
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Outline

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Objective: Stem cell based therapies for neurological disorders including brain tumors advance continuously towards clinical trials. Optimized cell delivery to the brain remains a challenge since transplantation efficiency after direct cerebral cell injection is very low. We investigated the feasibility of intranasal administration (INA) of neural stem/progenitor cells (NSPC) as an alternative, non-invasive and direct passage for the delivery of stem cells in treating malignant glioma.

Methods: Murine eGFP-NSPC and human HB1.F3 cells were intranasally administered as nose drops in two murine orthotopic glioma models (U87 & G55T2, n=21). Specific tumor targeting of NSPC and migratory pathways were investigated in a histological time series analysis of brains, olfactory structures, trigeminal nerves and peripheral organs (n=20). 7-Tesla MR-imaging after intranasal application of iron-superoxide-particle-labelled (SPIO) HB1.F3 cells was conducted to visualize migratory routes and intracerebral cell accumulation in-vivo (n=6).

Results: Intranasally administered NSPC displayed a rapid, targeted tumor tropism with NSPC accumulating at the intracerebral glioma site within six hours after application. Histological time series analysis revealed NSPC to migrate either via the olfactory pathway consisting of nasal mucosa, olfactory bulb and olfactory tract to reach intracerebral glioma or to be distributed over the circulation making use of tumor neovasculature to enrich extensively at the glioma site. Mean numbers of cell accumulation in G55T2 tumors were 50±16 NSPC/mm2 intra- and 46±14 NSPC/mm2 peritumoral. For U87 tumors, a mean of 54±13 NSPC/mm2 intra- and 49±11 NSPC/mm2 peritumoral were detected seven days after INA. MR-imaging confirmed targeted tumor tropism of NSPC with exclusive intra- and peritumoral accumulation of SPIO-labelled human neural stem cells after intranasal application. NSPC counts significantly increased 24 h after INA, remaining on a stable plateau afterwards.

Conclusions: Intranasal application of NSPC leads to a rapid, targeted migration of cells towards intracerebral glioma. The distinct distribution of cells accumulating intra- and peritumoral makes INA a promising, non invasive alternative application of stem cells in the treatment of malignant glioma with the possibility of repeated delivery.