Ischemic brain injury: a consortium analysis of key factors involved in mesenchymal stem cell-mediated inflammatory reduction.
Citation:
McGuckin CP, Jurga M, Miller AM, Sarnowska A, Wiedner M, Boyle NT, Lynch MA, Jablonska A, Drela K, Lukomska B, Domanska-Janik K, Kenner L, Moriggl R, Degoul O, Perruisseau-Carrier C, Forraz N, Ischemic brain injury: a consortium analysis of key factors involved in mesenchymal stem cell-mediated inflammatory reduction., Archives of biochemistry and biophysics, 534, 1-2, 2013, 88-97Download Item:
Abstract:
Increasing global birth rate, coupled with the aging population surviving into their eighth decade has lead 26
to increased incidence diseases, hitherto designated as rare. Brain related ischemia, at birth, or later in 27
life, during, for example stroke, is increasing in global prevalence. Reactive microglia can contribute to 28
neuronal damage as well as compromising transplantion. One potential treatment strategy is cellular 29
therapy, using mesenchymal stem cells (hMSCs), which possess immunomodulatory and cell repair prop- 30
erties. For effective clinical therapy, mechanisms of action must be understood better. Here multicentre 31
international laboratories assessed this question together investigating application of hMSCs neural 32
involvement, with interest in the role of reactive microglia. Modulation by hMSCs in our in vivo and in 33
vitro study shows they decrease markers of microglial activation (lower ED1 and Iba) and astrogliosis 34
(lower GFAP) following transplantation in an ouabain-induced brain ischemia rat model and in organo- 35
typic hippocampal cultures. The anti-inflammatory effect in vitro was demonstrated to be CD200 ligand 36
dependent with ligand expression shown to be increased by IL-4 stimulation. hMSC transplant reduced 37
ratmicroglial STAT3 gene expression and reduced activation of Y705 phosphorylated STAT3, but STAT3 in 38
the hMSCs themselves was elevated upon grafting. Surprisingly, activity was dependent on heterodimer- 39
isation with STAT1 activated by IL-4 and Oncostatin M. Our study paves the way to preclinical stages of a 40
clinical trial with hMSC, and suggests a non-canonical JAK-STAT signaling of unphosphorylated STAT3 in 41
immunomodulatory effects of hMSCs.
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http://people.tcd.ie/lynchmaDescription:
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Author: LYNCH, MARINA ANNETTA
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Journal ArticleCollections
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Archives of biochemistry and biophysics534
1-2
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JAK-STAT signalingMetadata
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