gms | German Medical Science

58. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e. V. (DGNC)

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

26. bis 29.04.2007, Leipzig

A murine model of myoblast-mediated gene therapy for the brain

Ein Myoblasten-Modell von Gehirn-Gen-Therapie in der Maus

Meeting Abstract

  • corresponding author P.G. Peña-Tapia - Klinik für Neurochirurgie, Klinikum Mannheim, Universität Heidelberg
  • J. Woitzik - Klinik für Neurochirurgie, Klinikum Mannheim, Universität Heidelberg
  • M. Vinci - Klinik für Neurochirurgie, Klinikum Mannheim, Universität Heidelberg
  • H. Blau - Baxter Laboratory in Genetic Pharmacology, Stanford University School of Medicine, Stanford, USA
  • P. Vajkoczy - Klinik für Neurochirurgie, Klinikum Mannheim, Universität Heidelberg

Deutsche Gesellschaft für Neurochirurgie. 58. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC). Leipzig, 26.-29.04.2007. Düsseldorf: German Medical Science GMS Publishing House; 2007. DocP 092

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dgnc2007/07dgnc347.shtml

Veröffentlicht: 11. April 2007

© 2007 Peña-Tapia et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Objective: The DNA transfer to somatic cells in order to achieve an overexpression of available proteins or expression of new ones, represents a new and innovative drug delivery strategy. In the Brain, a continuos delivery of molecules may be attractive for the treatment of ischemic brain diseases, degenerative diseases, and brain tumors. The aim of the present study was to use the temporalis muscle as the target for DNA transfer, following the idea that the transfected muscle cells may serve as future source for continuous drug delivery to the cerebral cortex.

Methods: 18 C57/BL6 mice were asigned to 3 different myoblast implantation modalities: A) intramuscular injection in the internal surface of the disected temporal muscle, B) application as cell pellet placed onto the surface of the temporalis muscle, and C) a combination of modalities A and B. For gene transfer, LacZ myoblasts were implanted into the temporalis muscle once an encephalomyosinangiosis model was established. At day 14 the mice were sacrificed. Fusion rate and β-Galactosidase expression were analysed.

Results: Myoblasts were successfully implanted in all cases. No significant inflamatory response was found. The hybrid myofibers (β-Galactosidase positive) were evident among the normal muscle architecture. The percentage of LacZ positive surface (transfected muscle fibers + free myoblasts) was 8,8±5,2 mm2 in group A, 13,3±9,6 mm2 in group B, and 11,8±3,2 mm2 in group C. In group A the mean number of LacZ positive myofibers was 58,8±28,2; in group B 36,8±30.3 and in group C 60,1±23,3. No statistical differences between groups were found.

Conclusions: The presented model constitutes a feasible, new, not inmunogenic and reproducible method of gene therapy of the temporalis muscle, that could allow the constant long-term delivery of considerable amounts of different biologically active substances to the brain. Although the differences between the implantation techniques were not statistically signigficant, the number of hybrid myofibers (therapeutically relevant), was higher in the combined application group, therefore we consider this implantation technique as the more appropriate for this kind of experimental model.