BDNF gene-modified mesenchymal stem cells promote functional recovery and reduce infarct size in the rat middle cerebral artery occlusion model

Kazuhiko Kurozumi, Kiminori Nakamura, Takashi Tamiya, Yutaka Kawano, Masayoshi Kobune, Sachie Hirai, Hiroaki Uchida, Katsunori Sasaki, Yoshinori Ito, Kazunori Kato, Osamu Honmou, Kiyohiro Houkin, Isao Date, Hirofumi Hamada

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Abstract

Examination of the clinical therapeutic efficacy of using bone marrow stromal cells, including mesenchymal stem cells (MSC), has recently been the focus of much investigation. MSC were reported to ameliorate functional deficits after stroke in rats, with some of this improvement possibly resulting from the action of cytokines secreted by these cells. To enhance such cytokine effects, we transfected telomerized human MSC with the BDNF gene using a fiber-mutant F/RGD adenovirus vector and investigated whether these cells contributed to improved functional recovery in a rat transient middle cerebral artery occlusion (MCAO) model. BDNF production by MSC-BDNF cells was 23-fold greater than that seen in uninfected MSC. Rats that received MSC-BDNF showed significantly more functional recovery than did control rats following MCAO. Specifically, MRI analysis revealed that the rats in the MSC-BDNF group exhibited more significant recovery from ischemia after 7 and 14 days. The number of TUNEL-positive cells in the ischemic boundary zone was significantly smaller in animals treated with MSC-BDNF compared to animals in the control group. These data suggest that MSC transfected with the BDNF gene may be useful in the treatment of cerebral ischemia and may represent a new strategy for the treatment of stroke.

Original languageEnglish
Pages (from-to)189-197
Number of pages9
JournalMolecular Therapy
Volume9
Issue number2
DOIs
Publication statusPublished - Feb 2004

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Middle Cerebral Artery Infarction
Brain-Derived Neurotrophic Factor
Mesenchymal Stromal Cells
Genes
Stroke
Cytokines
In Situ Nick-End Labeling
Brain Ischemia
Adenoviridae
Ischemia
Control Groups

Keywords

  • Adenoviral vector
  • BDNF
  • Cerebral infarction
  • Gene therapy
  • Mesenchymal stem cell
  • MRI

ASJC Scopus subject areas

  • Molecular Biology

Cite this

BDNF gene-modified mesenchymal stem cells promote functional recovery and reduce infarct size in the rat middle cerebral artery occlusion model. / Kurozumi, Kazuhiko; Nakamura, Kiminori; Tamiya, Takashi; Kawano, Yutaka; Kobune, Masayoshi; Hirai, Sachie; Uchida, Hiroaki; Sasaki, Katsunori; Ito, Yoshinori; Kato, Kazunori; Honmou, Osamu; Houkin, Kiyohiro; Date, Isao; Hamada, Hirofumi.

In: Molecular Therapy, Vol. 9, No. 2, 02.2004, p. 189-197.

Research output: Contribution to journalArticle

Kurozumi, K, Nakamura, K, Tamiya, T, Kawano, Y, Kobune, M, Hirai, S, Uchida, H, Sasaki, K, Ito, Y, Kato, K, Honmou, O, Houkin, K, Date, I & Hamada, H 2004, 'BDNF gene-modified mesenchymal stem cells promote functional recovery and reduce infarct size in the rat middle cerebral artery occlusion model', Molecular Therapy, vol. 9, no. 2, pp. 189-197. https://doi.org/10.1016/j.ymthe.2003.10.012
Kurozumi, Kazuhiko ; Nakamura, Kiminori ; Tamiya, Takashi ; Kawano, Yutaka ; Kobune, Masayoshi ; Hirai, Sachie ; Uchida, Hiroaki ; Sasaki, Katsunori ; Ito, Yoshinori ; Kato, Kazunori ; Honmou, Osamu ; Houkin, Kiyohiro ; Date, Isao ; Hamada, Hirofumi. / BDNF gene-modified mesenchymal stem cells promote functional recovery and reduce infarct size in the rat middle cerebral artery occlusion model. In: Molecular Therapy. 2004 ; Vol. 9, No. 2. pp. 189-197.
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