Behavioral and histological evaluation of a focal cerebral infarction rat model transplanted with neurons induced from bone marrow stromal cells

Toshiro Mimura, Mari Dezawa, Hiroshi Kanno, Isao Yamamoto

Research output: Contribution to journalArticlepeer-review

59 Citations (Scopus)

Abstract

Neurons can be specifically induced from bone marrow stromal cells (MSCs) with extremely high efficiency using gene transfection of the Notch intracellular domain and subsequent treatment with basic-fibroblast growth factor, forskolin, and ciliary neurotrophic factor. We investigated the behavioral and histologic efficacy of such bone marrow stromal cell-derived neuronal cell (MSDNC) transplantation into a focal cerebral infarction model in rats. A left middle cerebral artery occlusion (MCAO) was performed on adult Wistar rats. MSDNC transplantation into the ipsilateral hemisphere was performed on day 7 after MCAO. The behavioral analyses were conducted on days 14, 21, 28, 35, and 36-40, and a histologic evaluation was performed on day 41. MSDNC-transplanted rats showed significant recovery compared with controls (MCAO without cell transplantation) in beam balance, limb placing, and Morris water maze tests. Histologically, transplanted cells migrated from the injection site into the ischemic boundary area, including the cortex, corpus callosum, striatum, and hippocampus. Transplanted MSDNCs were positive for MAP-2 (84% ± 8.11%), whereas only a small number of cells were positive for GFAP (1.0% ± 0.23%). The survival rates of MSDNCs and MSCs 1 month after transplantation were approximately 45% and 10%, respectively. These results suggest that use of MSDNCs may be a promising therapeutic strategy for cerebral infarction.

Original languageEnglish
Pages (from-to)1108-1117
Number of pages10
JournalJournal of Neuropathology and Experimental Neurology
Volume64
Issue number12
DOIs
Publication statusPublished - 2005 Dec

Keywords

  • Behavioral analysis
  • Bone marrow stromal cell
  • Immunohistochemistry
  • Middle cerebral artery occlusion (MCAO)
  • Transplantation

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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