Bone marrow stromal cells that enhanced fibroblast growth factor-2 secretion by herpes simplex virus vector improve neurological outcome after transient focal cerebral ischemia in rats

Naokado Ikeda, Naosuke Nonoguchi, Zhu Zhao Ming, Takuji Watanabe, Yoshinaga Kajimoto, Daisuke Furutama, Fumiharu Kimura, Mari Dezawa, Robert S. Coffin, Yoshinori Otsuki, Toshihiko Kuroiwa, Shin Ichi Miyatake

Research output: Contribution to journalArticlepeer-review

99 Citations (Scopus)

Abstract

Background and Purpose - Fibroblast growth factor-2 (FGF-2) administration and bone marrow stromal cell (MSC) transplantation could improve neurological deficits after occlusive cerebrovascular disease. In the present study, we examined the effects of neurological improvement after transient middle cerebral artery occlusion (MCAO) in rats by a novel therapeutic strategy with FGF-2 gene-transferred MSCs by the herpes simplex virus type 1 (HSV-1) vector. Methods - Adult Wistar rats were anesthetized. Nonmodified MSCs, FGF-2-modified MSCs with HSV-1 1764/-4/pR19/ ssIL2-FGF-2, or PBS was administered intracerebrally 24 hours after transient right MCAO. All animals underwent behavioral tests for 21 days, and the infarction volume with 2-3-5-triphenylterazolium was detected 3 days and 14 days after the MCAO. Three days and 7 days after the MCAO, the FGF-2 production in the ipsilateral hemisphere of the MCAO was measured with ELISA. Seven and 14 days after the MCAO, immunohistochemical staining for FGF-2 was applied. Results - The stroke animals receiving FGF-2-modified MSCs demonstrated significant functional recovery compared with the other groups. Fourteen days after the MCAO, there was a significant reduction in infarction volume only in FGF-2-modified MSC-treated group. FGF-2 production in the FGF-2-modified MSC-treated brain was significantly higher compared with the other groups at 3 and 7 days after MCAO. Administrated FGF-2-modified MSCs strongly expressed the FGF-2 protein, which was proven by ELISA. Conclusions - Our data suggest that the FGF-2 gene-modified MSCs with the HSV-1 vector can contribute to remarkable functional recovery after stroke compared with MSCs transplantation alone.

Original languageEnglish
Pages (from-to)2725-2730
Number of pages6
JournalStroke
Volume36
Issue number12
DOIs
Publication statusPublished - 2005 Dec

Keywords

  • Bone marrow cell
  • Cerebral infarct
  • FGF-2
  • Hsv-1 vector

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialised Nursing

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