PMID- 29569981
OWN - NLM
STAT- MEDLINE
DCOM- 20200526
LR  - 20200901
IS  - 1559-7016 (Electronic)
IS  - 0271-678X (Print)
IS  - 0271-678X (Linking)
VI  - 39
IP  - 9
DP  - 2019 Sep
TI  - Regulatory T-cells within bone marrow-derived stem cells actively confer 
      immunomodulatory and neuroprotective effects against stroke.
PG  - 1750-1758
LID - 10.1177/0271678X18766172 [doi]
AB  - Regulatory T-cells (T(regs)) may exert a neuroprotective effect on ischemic 
      stroke by inhibiting both inflammation and effector T-cell activation. 
      Transplantation of human bone marrow-derived stem cells (BMSCs) in ischemic 
      stroke affords neuroprotection that results in part from the cells' 
      anti-inflammatory property. However, the relationship between T(regs) and BMSCs 
      in treatment of ischemic stroke has not been fully elucidated. Here, we tested 
      the hypothesis that T(regs) within the BMSCs represent active mediators of 
      immunomodulation and neuroprotection in experimental stroke. Primary rat neuronal 
      cells were subjected to an oxygen-glucose deprivation and reperfusion (OGD/R) 
      condition. The cells were re-perfused and co-cultured with T(regs) and/or BMSCs. 
      We detected a minority population of T(regs) within BMSCs with both 
      immunocytochemistry (ICC) and flow cytometry identifying cells expressing 
      phenotypic markers of CD4, CD25, and FoxP3 protein. BMSCs with the native 
      population of T(regs) conferred maximal neuroprotection compared to the treatment 
      conditions containing 0%, 10%, and 100% relative ratio T(regs). Increasing the 
      T(reg) population resulted in increased IL6 secretion and decreased FGF-beta 
      secretion by BMSCs. This study shows that a minority population of T(regs) exists 
      within the therapeutic BMSC population, which serves as robust mediators of the 
      immunomodulatory and neuroprotective effect provided by BMSC transplantation.
FAU - Neal, Elliot G
AU  - Neal EG
AD  - 1 Department of Neurosurgery and Brain Repair, Center of Excellence for Aging and 
      Brain Repair, USF Morsani College of Medicine, Tampa, FL, USA.
FAU - Acosta, Sandra A
AU  - Acosta SA
AD  - 1 Department of Neurosurgery and Brain Repair, Center of Excellence for Aging and 
      Brain Repair, USF Morsani College of Medicine, Tampa, FL, USA.
FAU - Kaneko, Yuji
AU  - Kaneko Y
AD  - 1 Department of Neurosurgery and Brain Repair, Center of Excellence for Aging and 
      Brain Repair, USF Morsani College of Medicine, Tampa, FL, USA.
FAU - Ji, Xunming
AU  - Ji X
AD  - 2 Cerebrovascular Research Center, XuanWu Hospital, Capital Medical University, 
      Beijing, China.
FAU - Borlongan, Cesario V
AU  - Borlongan CV
AD  - 1 Department of Neurosurgery and Brain Repair, Center of Excellence for Aging and 
      Brain Repair, USF Morsani College of Medicine, Tampa, FL, USA.
LA  - eng
GR  - R01 NS071956/NS/NINDS NIH HHS/United States
GR  - R01 NS090962/NS/NINDS NIH HHS/United States
GR  - R21 NS089851/NS/NINDS NIH HHS/United States
GR  - R21 NS094087/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20180323
PL  - United States
TA  - J Cereb Blood Flow Metab
JT  - Journal of cerebral blood flow and metabolism : official journal of the 
      International Society of Cerebral Blood Flow and Metabolism
JID - 8112566
RN  - 0 (Cytokines)
SB  - IM
MH  - Adaptive Immunity
MH  - Animals
MH  - Brain Ischemia/immunology/therapy
MH  - Cells, Cultured
MH  - Cytokines/immunology
MH  - Humans
MH  - Immunomodulation
MH  - Male
MH  - *Mesenchymal Stem Cell Transplantation
MH  - Mesenchymal Stem Cells/*immunology
MH  - Mice, Inbred C57BL
MH  - Neuroprotection
MH  - Rats
MH  - Stroke/immunology/*therapy
MH  - T-Lymphocytes, Regulatory/*immunology
PMC - PMC6727132
OTO - NOTNLM
OT  - Adaptive immunity
OT  - foxp3
OT  - immunotherapy
OT  - ischemia
EDAT- 2018/03/24 06:00
MHDA- 2020/05/27 06:00
PMCR- 2020/09/01
CRDT- 2018/03/24 06:00
PHST- 2018/03/24 06:00 [pubmed]
PHST- 2020/05/27 06:00 [medline]
PHST- 2018/03/24 06:00 [entrez]
PHST- 2020/09/01 00:00 [pmc-release]
AID - 10.1177_0271678X18766172 [pii]
AID - 10.1177/0271678X18766172 [doi]
PST - ppublish
SO  - J Cereb Blood Flow Metab. 2019 Sep;39(9):1750-1758. doi: 
      10.1177/0271678X18766172. Epub 2018 Mar 23.