PMID- 20936694
OWN - NLM
STAT- MEDLINE
DCOM- 20110303
LR  - 20181201
IS  - 1097-4547 (Electronic)
IS  - 0360-4012 (Linking)
VI  - 88
IP  - 16
DP  - 2010 Dec
TI  - Transplantation of neuronal cells induced from human mesenchymal stem cells 
      improves neurological functions after stroke without cell fusion.
PG  - 3598-609
LID - 10.1002/jnr.22501 [doi]
AB  - The options for treating stroke are limited, but stem cells hold promise as a 
      therapy because of their multipotency. Neuronal cells derived from mesenchymal 
      stem cells (MSC) were reported to have more therapeutic effect than MSCs. For 
      elucidating the therapeutic mechanism of neuronal cells, here we generated a 
      model of focal cerebral infarction by performing left common carotid artery 
      occlusion in adult gerbils. We transfected human trabecular bone-derived MSCs 
      (hMSCs) with the Notch intracellular domain to induce their differentiation into 
      neuronal cells (hN-MSCs). These cells were stereotaxically transplanted into the 
      local ischemic hemisphere 4 days after the occlusion. Behavioral analyses were 
      conducted 28 days after transplantation, and then fluorescence in situ 
      hybridization (FISH) and a histological evaluation were performed. 
      Histologically, transplanted cells were distributed around the periinfarct 
      region, and approximately 8.5% and 4.2% of hN-MSCs and hMSCs survived, 
      respectively; 53.2% +/- 9.6% of hN-MSCs were microtubule-associated protein 2(+) 
      (MAP-2(+) ) and extended neurites, whereas only 0.9% +/- 0.3% of hMSCs were 
      MAP-2(+) . In FISH, human nucleus-specific signals were detected in both hN-MSCs 
      and hMSCs grafted brains, but no transplanted cell had a merged gerbil-specific 
      nuclear signals. hN-MSC-transplanted animals showed significantly better recovery 
      than animals given control vehicle in the T-maze, bilateral asymmetry, and open 
      field tests. These findings suggested that hN-MSCs have greater therapeutic 
      potential than hMSCs for stroke and that cell fusion does not primarily 
      contribute to the therapeutic mechanism of MSC transplantation.
CI  - Copyright (c) 2010 Wiley-Liss, Inc.
FAU - Xu, Haiyan
AU  - Xu H
AD  - Department of Neurology and Neurological Science, Graduate School of Medicine, 
      Tokyo Medical and Dental University, Tokyo, Japan.
FAU - Miki, Kazunori
AU  - Miki K
FAU - Ishibashi, Satoru
AU  - Ishibashi S
FAU - Inoue, Jun
AU  - Inoue J
FAU - Sun, Liyuan
AU  - Sun L
FAU - Endo, Shu
AU  - Endo S
FAU - Sekiya, Ichiro
AU  - Sekiya I
FAU - Muneta, Takeshi
AU  - Muneta T
FAU - Inazawa, Joji
AU  - Inazawa J
FAU - Dezawa, Mari
AU  - Dezawa M
FAU - Mizusawa, Hidehiro
AU  - Mizusawa H
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20101008
PL  - United States
TA  - J Neurosci Res
JT  - Journal of neuroscience research
JID - 7600111
RN  - 0 (Receptors, Notch)
SB  - IM
MH  - Animals
MH  - Cell Differentiation/physiology
MH  - Cell Fusion
MH  - *Cell Transplantation
MH  - Cerebral Infarction/complications/pathology
MH  - Cerebrum/pathology/*surgery
MH  - Disease Models, Animal
MH  - Gerbillinae
MH  - Humans
MH  - Male
MH  - Maze Learning/physiology
MH  - Mesenchymal Stem Cells/*cytology
MH  - Neurites/physiology
MH  - Neurons/*cytology/physiology
MH  - Receptors, Notch/genetics/physiology
MH  - Recovery of Function/physiology
MH  - Stroke/etiology/pathology/*surgery
MH  - Transfection
MH  - Transplantation, Heterologous
EDAT- 2010/10/12 06:00
MHDA- 2011/03/04 06:00
CRDT- 2010/10/12 06:00
PHST- 2010/02/11 00:00 [received]
PHST- 2010/06/26 00:00 [revised]
PHST- 2010/07/22 00:00 [accepted]
PHST- 2010/10/12 06:00 [entrez]
PHST- 2010/10/12 06:00 [pubmed]
PHST- 2011/03/04 06:00 [medline]
AID - 10.1002/jnr.22501 [doi]
PST - ppublish
SO  - J Neurosci Res. 2010 Dec;88(16):3598-609. doi: 10.1002/jnr.22501. Epub 2010 Oct 
      8.