PMID- 24633139
OWN - NLM
STAT- MEDLINE
DCOM- 20150819
LR  - 20181202
IS  - 1552-6844 (Electronic)
IS  - 1545-9683 (Linking)
VI  - 29
IP  - 1
DP  - 2015 Jan
TI  - Bone marrow stromal cells rescue ischemic brain by trophic effects and phenotypic 
      change toward neural cells.
PG  - 80-9
LID - 10.1177/1545968314525856 [doi]
AB  - Background. Transplantation of bone marrow stromal cells (BMSCs) may contribute 
      to functional recovery after stroke. This study was designed to clarify their 
      mechanisms, trophic effects of neurotrophic factors, and neural differentiation. 
      Methods. Mouse neurons exposed to glutamate were cocultured with mouse BMSCs. 
      Either neutralizing antibodies against brain-derived neurotrophic factor (BDNF) 
      or nerve growth factor (NGF) or Trk inhibitor K252a was added to explore the 
      mechanism of their protective effects. Fluorescence in situ hybridization (FISH) 
      was used to assess BDNF or NGF mRNA expression in BMSCs. The mice were subjected 
      to permanent focal ischemia, and 7 days later, either BMSCs or the vehicle was 
      stereotactically transplanted into the ipsilateral striatum. The mouse brains 
      were processed for FISH and immunostaining 2 or 4 weeks after transplantation. 
      Results. BMSCs significantly ameliorated glutamate-induced neuronal death. 
      Treatment with anti-BDNF antibody significantly reduced their protective effects. 
      FISH analysis showed that the majority of BMSCs expressed BDNF and NGF mRNA in 
      vitro. BMSC transplantation significantly improved the survival of neurons in 
      peri-infarct areas. FISH analysis revealed that approximately half of BMSCs 
      expressed BDNF and NGF mRNA 2 weeks after transplantation; however, the 
      percentage of BDNF and NGF mRNA-positive cells decreased thereafter. Instead, the 
      percentage of microtubule-associated protein 2-positive BMSCs gradually increased 
      during 4 weeks after transplantation. Conclusions. These findings strongly 
      suggest that BDNF may be a key factor underlying the trophic effects of BMSCs. 
      BMSCs might exhibit the trophic effect in the early stage of cell therapy and the 
      phenotypic change toward neural cells thereafter.
CI  - (c) The Author(s) 2014.
FAU - Shichinohe, Hideo
AU  - Shichinohe H
AD  - Depertment of Neurosurgery, Hokkaido University Graduate School of Medicine, 
      Sapporo, Japan.
FAU - Ishihara, Takeshi
AU  - Ishihara T
AD  - Shionogi Innovation Center for Drug, Shionogi & Co Ltd, Sapporo, Japan.
FAU - Takahashi, Koji
AU  - Takahashi K
AD  - Shionogi Innovation Center for Drug, Shionogi & Co Ltd, Sapporo, Japan.
FAU - Tanaka, Yoshikazu
AU  - Tanaka Y
AD  - Shionogi Innovation Center for Drug, Shionogi & Co Ltd, Sapporo, Japan.
FAU - Miyamoto, Michiyuki
AU  - Miyamoto M
AD  - Depertment of Neurosurgery, Hokkaido University Graduate School of Medicine, 
      Sapporo, Japan.
FAU - Yamauchi, Tomohiro
AU  - Yamauchi T
AD  - Depertment of Neurosurgery, Hokkaido University Graduate School of Medicine, 
      Sapporo, Japan.
FAU - Saito, Hisayasu
AU  - Saito H
AD  - Depertment of Neurosurgery, Hokkaido University Graduate School of Medicine, 
      Sapporo, Japan.
FAU - Takemoto, Hiroshi
AU  - Takemoto H
AD  - Shionogi Innovation Center for Drug, Shionogi & Co Ltd, Sapporo, Japan.
FAU - Houkin, Kiyohiro
AU  - Houkin K
AD  - Depertment of Neurosurgery, Hokkaido University Graduate School of Medicine, 
      Sapporo, Japan.
FAU - Kuroda, Satoshi
AU  - Kuroda S
AD  - Department of Neurosurgery, Graduate School of Medicine and Pharmaceutical 
      Science for Education, University of Toyama, Toyama, Japan 
      skuroda@med.u-toyama.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140314
PL  - United States
TA  - Neurorehabil Neural Repair
JT  - Neurorehabilitation and neural repair
JID - 100892086
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (enhanced green fluorescent protein)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - 9061-61-4 (Nerve Growth Factor)
RN  - EC 4.2.1.11 (Phosphopyruvate Hydratase)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/genetics/*metabolism
MH  - Cell Count
MH  - Cells, Cultured
MH  - Cerebral Cortex/cytology
MH  - Coculture Techniques
MH  - Disease Models, Animal
MH  - Embryo, Mammalian
MH  - Green Fluorescent Proteins/genetics/metabolism
MH  - Imaging, Three-Dimensional
MH  - Infarction, Middle Cerebral Artery/*surgery
MH  - Male
MH  - Mesenchymal Stem Cell Transplantation/*methods
MH  - Mesenchymal Stem Cells/*physiology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Transgenic
MH  - Microtubule-Associated Proteins/metabolism
MH  - Nerve Growth Factor/genetics/*metabolism
MH  - Neurons/metabolism
MH  - Phosphopyruvate Hydratase/*metabolism
MH  - RNA, Messenger/metabolism
OTO - NOTNLM
OT  - bone marrow stromal cells
OT  - coculture
OT  - neurotrophic factor
OT  - permanent middle cerebral artery occlusion
OT  - regenerative medicine
EDAT- 2014/03/19 06:00
MHDA- 2015/08/20 06:00
CRDT- 2014/03/18 06:00
PHST- 2014/03/18 06:00 [entrez]
PHST- 2014/03/19 06:00 [pubmed]
PHST- 2015/08/20 06:00 [medline]
AID - 1545968314525856 [pii]
AID - 10.1177/1545968314525856 [doi]
PST - ppublish
SO  - Neurorehabil Neural Repair. 2015 Jan;29(1):80-9. doi: 10.1177/1545968314525856. 
      Epub 2014 Mar 14.