PMID- 23759293
OWN - NLM
STAT- MEDLINE
DCOM- 20140423
LR  - 20181202
IS  - 1095-953X (Electronic)
IS  - 0969-9961 (Linking)
VI  - 58
DP  - 2013 Oct
TI  - Immune following suppression mesenchymal stem cell transplantation in the 
      ischemic brain is mediated by TGF-beta.
PG  - 249-57
LID - S0969-9961(13)00168-X [pii]
LID - 10.1016/j.nbd.2013.06.001 [doi]
AB  - Transplantation of mesenchymal stem cells (MSCs) has been shown to enhance the 
      recovery of brain functions following ischemic injury. Although immune modulation 
      has been suggested to be one of the mechanisms, the molecular mechanisms 
      underlying improved recovery has not been clearly identified. Here, we report 
      that MSCs secrete transforming growth factor-beta (TGF-beta) to suppress immune 
      propagation in the ischemic rat brain. Ischemic stroke caused global death of 
      resident cells in the infarcted area, elevated the monocyte chemoattractant 
      protein-1 (MCP-1) level, and evoked massive infiltration of circulating CD68+ 
      immune cells through the impaired blood-brain barrier. Transplantation of MSCs at 
      day 3 post-ischemia blocked the subsequent upregulation of MCP-1 in the ischemic 
      area and the infiltration of additional CD68+ immune cells. MSC-conditioned media 
      decreased the migration and MCP-1 production of freshly isolated immune cells in 
      vitro, and this effect was blocked by an inhibitor of TGF-beta signaling or an 
      anti-TGF-beta neutralizing antibody. Finally, transplantation of TGF-beta1-silenced 
      MSCs failed to attenuate the infiltration of CD68+ cells into the ischemic brain, 
      and was associated with only minor improvements in motor function. These results 
      indicate that TGF-beta is key to the ability of MSCs to beneficially attenuate 
      immune reactions in the ischemic brain. Our findings offer insight into the 
      interactions between allogeneic MSCs and the host immune system, reinforcing the 
      prospective clinical value of using MSCs in the treatment of neurological 
      disorders involving inflammation-mediated secondary damage.
CI  - Copyright (c) 2013. Published by Elsevier Inc.
FAU - Yoo, Seung-Wan
AU  - Yoo SW
AD  - Department of Anatomy, Ajou University School of Medicine, Suwon, South Korea.
FAU - Chang, Da-Young
AU  - Chang DY
FAU - Lee, Hye-Sun
AU  - Lee HS
FAU - Kim, Gyu-Hee
AU  - Kim GH
FAU - Park, Jin-Sung
AU  - Park JS
FAU - Ryu, Buom-Yong
AU  - Ryu BY
FAU - Joe, Eun-Hye
AU  - Joe EH
FAU - Lee, Young-Don
AU  - Lee YD
FAU - Kim, Sung-Soo
AU  - Kim SS
FAU - Suh-Kim, Haeyoung
AU  - Suh-Kim H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130610
PL  - United States
TA  - Neurobiol Dis
JT  - Neurobiology of disease
JID - 9500169
RN  - 0 (Aif1 protein, rat)
RN  - 0 (Antigens, CD)
RN  - 0 (Calcium-Binding Proteins)
RN  - 0 (Ccl2 protein, rat)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Microfilament Proteins)
RN  - 0 (Transforming Growth Factor beta)
RN  - EC 1.11.1.7 (Peroxidase)
SB  - IM
MH  - Animals
MH  - Antigens, CD/metabolism
MH  - Blood-Brain Barrier/physiopathology
MH  - Brain Infarction/etiology
MH  - Calcium-Binding Proteins/metabolism
MH  - Cell Movement
MH  - Cells, Cultured
MH  - Chemokine CCL2/metabolism
MH  - Disease Models, Animal
MH  - Encephalitis/etiology
MH  - Gene Expression Regulation/immunology/physiology
MH  - Infarction, Middle Cerebral Artery/complications/*immunology/*surgery
MH  - Male
MH  - *Mesenchymal Stem Cell Transplantation
MH  - Mesenchymal Stem Cells/*metabolism
MH  - Microfilament Proteins/metabolism
MH  - Peroxidase/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Time Factors
MH  - Transforming Growth Factor beta/immunology/*metabolism
OTO - NOTNLM
OT  - Cell death
OT  - Inflammation
OT  - Mesenchymal stem cell
OT  - Microglia
OT  - Stroke
OT  - TGF-beta
EDAT- 2013/06/14 06:00
MHDA- 2014/04/24 06:00
CRDT- 2013/06/14 06:00
PHST- 2013/02/01 00:00 [received]
PHST- 2013/05/22 00:00 [revised]
PHST- 2013/06/01 00:00 [accepted]
PHST- 2013/06/14 06:00 [entrez]
PHST- 2013/06/14 06:00 [pubmed]
PHST- 2014/04/24 06:00 [medline]
AID - S0969-9961(13)00168-X [pii]
AID - 10.1016/j.nbd.2013.06.001 [doi]
PST - ppublish
SO  - Neurobiol Dis. 2013 Oct;58:249-57. doi: 10.1016/j.nbd.2013.06.001. Epub 2013 Jun 
      10.