PMID- 25747577
OWN - NLM
STAT- MEDLINE
DCOM- 20160208
LR  - 20181113
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 10
IP  - 3
DP  - 2015
TI  - Therapeutic effects of human multilineage-differentiating stress enduring (MUSE) 
      cell transplantation into infarct brain of mice.
PG  - e0116009
LID - 10.1371/journal.pone.0116009 [doi]
LID - e0116009
AB  - OBJECTIVE: Bone marrow stromal cells (BMSCs) are heterogeneous and their 
      therapeutic effect is pleiotropic. Multilineage-differentiating stress enduring 
      (Muse) cells are recently identified to comprise several percentages of BMSCs, 
      being able to differentiate into triploblastic lineages including neuronal cells 
      and act as tissue repair cells. This study was aimed to clarify how Muse and 
      non-Muse cells in BMSCs contribute to functional recovery after ischemic stroke. 
      METHODS: Human BMSCs were separated into stage specific embryonic 
      antigen-3-positive Muse cells and -negative non-Muse cells. Immunodeficient mice 
      were subjected to permanent middle cerebral artery occlusion and received 
      transplantation of vehicle, Muse, non-Muse or BMSCs (2.5x104 cells) into the 
      ipsilateral striatum 7 days later. RESULTS: Motor function recovery in BMSC and 
      non-Muse groups became apparent at 21 days after transplantation, but reached the 
      plateau thereafter. In Muse group, functional recovery was not observed for up to 
      28 days post-transplantation, but became apparent at 35 days 
      post-transplantation. On immunohistochemistry, only Muse cells were integrated 
      into peri-infarct cortex and differentiate into Tuj-1- and NeuN-expressing cells, 
      while negligible number of BMSCs and non-Muse cells remained in the peri-infarct 
      area at 42 days post-transplantation. CONCLUSIONS: These findings strongly 
      suggest that Muse cells and non-Muse cells may contribute differently to tissue 
      regeneration and functional recovery. Muse cells may be more responsible for 
      replacement of the lost neurons through their integration into the peri-infarct 
      cortex and spontaneous differentiation into neuronal marker-positive cells. 
      Non-Muse cells do not remain in the host brain and may exhibit trophic effects 
      rather than cell replacement.
FAU - Yamauchi, Tomohiro
AU  - Yamauchi T
AD  - Department of Neurosurgery, Hokkaido University Graduate School of Medicine, 
      Sapporo, Japan.
FAU - Kuroda, Yasumasa
AU  - Kuroda Y
AD  - Department of Stem Cell Biology and Histology, Graduate School of Medicine, 
      Tohoku University, Sendai, Japan.
FAU - Morita, Takahiro
AU  - Morita T
AD  - Department of Stem Cell Biology and Histology, Graduate School of Medicine, 
      Tohoku University, Sendai, Japan.
FAU - Shichinohe, Hideo
AU  - Shichinohe H
AD  - Department of Neurosurgery, Hokkaido University Graduate School of Medicine, 
      Sapporo, Japan.
FAU - Houkin, Kiyohiro
AU  - Houkin K
AD  - Department of Neurosurgery, Hokkaido University Graduate School of Medicine, 
      Sapporo, Japan.
FAU - Dezawa, Mari
AU  - Dezawa M
AD  - Department of Stem Cell Biology and Histology, Graduate School of Medicine, 
      Tohoku University, Sendai, Japan.
FAU - Kuroda, Satoshi
AU  - Kuroda S
AD  - Department of Neurosurgery, Hokkaido University Graduate School of Medicine, 
      Sapporo, Japan; Department of Neurosurgery, Graduate School of Medicine and 
      Pharmacological Science, University of Toyama, Toyama, Japan.
LA  - eng
PT  - Journal Article
DEP - 20150306
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
SB  - IM
MH  - Animals
MH  - *Cell Differentiation
MH  - *Cell Lineage
MH  - *Cell Transplantation
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, SCID
MH  - Stroke/pathology/*therapy
PMC - PMC4351985
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2015/03/10 06:00
MHDA- 2016/02/09 06:00
PMCR- 2015/03/06
CRDT- 2015/03/10 06:00
PHST- 2014/08/15 00:00 [received]
PHST- 2014/12/03 00:00 [accepted]
PHST- 2015/03/10 06:00 [entrez]
PHST- 2015/03/10 06:00 [pubmed]
PHST- 2016/02/09 06:00 [medline]
PHST- 2015/03/06 00:00 [pmc-release]
AID - PONE-D-14-36754 [pii]
AID - 10.1371/journal.pone.0116009 [doi]
PST - epublish
SO  - PLoS One. 2015 Mar 6;10(3):e0116009. doi: 10.1371/journal.pone.0116009. 
      eCollection 2015.