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

Growth factor (HGF, FGF2, VEGF) gene-modified bone marrow stromal cells improve neurological outcome after stroke in rats

Meeting Abstract

  • corresponding author N. Nonoguchi - Department of Neurosurgery, Osaka medical college, Takatsuki, Japan
  • M.Z. Zhao - Department of Neurosurgery, Osaka medical college, Takatsuki, Japan
  • N. Ikeda - Department of Neurosurgery, Osaka medical college, Takatsuki, Japan
  • Y. Kajimoto - Department of Neurosurgery, Osaka medical college, Takatsuki, Japan
  • S. Miyatake - Department of Neurosurgery, Osaka medical college, Takatsuki, Japan
  • T. Kuroiwa - Department of Neurosurgery, Osaka medical college, Takatsuki, Japan

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. DocP 06.90

The electronic version of this article is the complete one and can be found online at:

Published: May 8, 2006

© 2006 Nonoguchi et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.



Objective: Recent animal studies demonstrated that some kind of growth factors can ameliorate neurological deficits and bone marrow stromal cell (MSC) transplantation also can improve neurological function after ischemic stroke. Our purpose is to make sure if growth factor (HGF, FGF2, VEGF) gene-modified MSC can achieve further therapeutic effect against ischemic cerebral diseases than native MSC.

Methods: For gene modification of MSCs, we used a replication-incompetent herpes simplex virus type-1 (HSV-1) vector “1764/4-“ originated from wild type HSV-1 strain 17 and made replication deficient by deletion and point mutation in the ICP4, ICP34.5, and VP16. It has been confirmed that this vector has very high ability of gene transduction to MSC, about 70-75% at MOI 10 and 95% at MOI 50. In this study, we prepared three kinds of vectors expressing HGF, FGF-2, and VEGF by homologous recombination. After adult Wister rats were anesthetized, non-gene modified MSCs (native MSCs), HGF modified MSCs, FGF-2 modified MSCs, VEGF modified MSCs, and PBS was administered directly into the lesioned brain 24 hours after transient middle cerebral artery occlusion (MCAO). all the MSCs in each group were marked with bis-benzimide (Hoechest 33258) ex vivo before the transplantation to identify them. All animals underwent behavioral test for 14 days, and the infarction volume was checked with 2-3-5-triphenylterazolium 3 days and 14 days after the MCAO. Each growth factor production in the lesioned brain was measured by ELISA and immunohistological staining.

Results: At 14 days after MCAO, all groups treated with growth factor modified MSCs showed significant improvement in modified neurological severity score (mNSS) when compared with native MSC treated group or sham-operated group (p<0.05). Infarct volume also showed the apparent decrease in all gene modified MSC-treated groups (p<0.05). In HGF modified MSC-treated group, the MAP-2 positive cell percentage tends to increase and the TUNEL positive cell percentage decrease in the ischemic boundary zone.

Conclusions: Growth factor gene-modified MSCs can contribute to remarkable functional recovery after stroke compared with native MSC alone.