Embryonic neural stem cells transplanted in middle cerebral artery occlusion model of rats demonstrated potent therapeutic effects, compared to adult neural stem cells

Kazuya Takahashi, Takao Yasuhara, Tetsuro Shingo, Kenichiro Muraoka, Masahiro Kameda, Akira Takeuchi, Akimasa Yano, Kazuhiko Kurozumi, Takashi Agari, Yasuyuki Miyoshi, Kazushi Kinugasa, Isao Date

Research output: Contribution to journalArticle

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Abstract

Cell therapy using stem cells is awaited by stroke patients with impaired movement and cognitive functions, although intravenous alteplase-administration ameliorated outcomes of patients receiving the therapy within 3 h of onset. In this study, we explored the therapeutic effects of neural progenitor cells (NPC) upon middle cerebral artery occlusion (MCAO) model of rats with exploration of the differences between adult and embryonic NPCs in therapeutic effects. GFP-labeled adult or embryonic NPCs were transplanted for transient MCAO model of rats at 1h after reperfusion. Rats were examined behaviorally using limb placement test, rotarod test and cylinder test with neuroradiological assessment using magnetic resonance imaging (MRI). Consequently after euthanasia, rats were immunohistochemically investigated to explore graft survival and immune reaction. MRI of rats receiving NPCs revealed significant reduction of infarct volumes, compared to vehicle-treated rats with corresponding behavioral amelioration. The transplanted cells were surviving in rats receiving NPCs, although the number of embryonic NPCs was significantly higher than that of adult NPCs. Iba-1-positive inflammatory cells of rats receiving adult NPCs were prominent, compared to those receiving embryonic NPCs, which might be a rationale for the differences between rats receiving adult and embryonic NPCs in the number of surviving NPCs. On the contraries, adult NPCs surely demonstrated therapeutic effects with a few surviving cells, thus indicating that the therapeutic effects might be due to trophic/growth factor-secretion from transplanted NPCs, rather than replacement of damaged host neurons. Therapeutic effects of NPCs for MCAO model of rats were clarified in this study. Transplantation of NPCs will be a hopeful strategy for stroke patients, although further studies are required for the patient safety and underlying mechanisms.

Original languageEnglish
Pages (from-to)172-182
Number of pages11
JournalBrain Research
Volume1234
DOIs
Publication statusPublished - Oct 9 2008

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Adult Stem Cells
Neural Stem Cells
Middle Cerebral Artery Infarction
Therapeutic Uses
Embryonic Stem Cells
Stem Cells
Stroke
Rotarod Performance Test
Magnetic Resonance Imaging
Euthanasia
Tissue Plasminogen Activator
Graft Survival
Patient Safety
Cell- and Tissue-Based Therapy
Intravenous Administration
Cognition
Reperfusion
Intercellular Signaling Peptides and Proteins
Extremities
Transplantation

Keywords

  • Focal ischemia
  • Magnetic resonance imaging
  • Neural stem cell
  • Neuroprotection
  • Transplantation

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Developmental Biology
  • Molecular Biology

Cite this

Embryonic neural stem cells transplanted in middle cerebral artery occlusion model of rats demonstrated potent therapeutic effects, compared to adult neural stem cells. / Takahashi, Kazuya; Yasuhara, Takao; Shingo, Tetsuro; Muraoka, Kenichiro; Kameda, Masahiro; Takeuchi, Akira; Yano, Akimasa; Kurozumi, Kazuhiko; Agari, Takashi; Miyoshi, Yasuyuki; Kinugasa, Kazushi; Date, Isao.

In: Brain Research, Vol. 1234, 09.10.2008, p. 172-182.

Research output: Contribution to journalArticle

Takahashi, Kazuya ; Yasuhara, Takao ; Shingo, Tetsuro ; Muraoka, Kenichiro ; Kameda, Masahiro ; Takeuchi, Akira ; Yano, Akimasa ; Kurozumi, Kazuhiko ; Agari, Takashi ; Miyoshi, Yasuyuki ; Kinugasa, Kazushi ; Date, Isao. / Embryonic neural stem cells transplanted in middle cerebral artery occlusion model of rats demonstrated potent therapeutic effects, compared to adult neural stem cells. In: Brain Research. 2008 ; Vol. 1234. pp. 172-182.
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