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@ARTICLE{PrezMato:859963,
      author       = {Pérez-Mato, María and Iglesias-Rey, Ramón and
                      Vieites-Prado, Alba and Dopico-López, Antonio and Argibay,
                      Bárbara and Fernández-Susavila, Héctor and da
                      Silva-Candal, Andrés and Pérez-Díaz, Amparo and
                      Correa-Paz, Clara and Günther, Anne and Ávila-Gómez,
                      Paulo and Isabel Loza, M. and Baumann, A. and Castillo,
                      José and Sobrino, Tomás and Campos, Francisco},
      title        = {{B}lood glutamate {EAAT}2-cell grabbing therapy in cerebral
                      ischemia},
      journal      = {EBioMedicine},
      volume       = {39},
      issn         = {2352-3964},
      address      = {Amsterdam [u.a.]},
      publisher    = {Elsevier},
      reportid     = {FZJ-2019-00769},
      pages        = {118-131},
      year         = {2019},
      abstract     = {BackgroundExcitatory amino acid transporter 2 (EAAT2) plays
                      a pivotal role in glutamate clearance in the adult brain,
                      thereby preventing excitotoxic effects. Considering the high
                      efficacy of EAAT2 for glutamate uptake, we hypothesized that
                      the expression of this transporter in mesenchymal stem cells
                      (MSCs) for systemic administration could yield a cell-based
                      glutamate-grabbing therapy, combining the intrinsic
                      properties of these cells with excitotoxic
                      protection.MethodsTo address this hypothesis, EAAT2-encoding
                      cDNA was introduced into MSCs and human embryonic kidney 293
                      cells (HEK cells) as the control cell line. EAAT2 expression
                      and functionality were evaluated by in vitro assays. Blood
                      glutamate-grabbing activity was tested in healthy and
                      ischemic rat models treated with 3 × 106 and
                      9 × 106 cells/animal.FindingsThe expression of EAAT2 in
                      both cell types conferred the expected glutamate-grabbing
                      activity in in vitro and in vivo studies. The functional
                      improvement observed in ischemic rats treated with
                      EAAT2–HEK at low dose, confirmed that this effect was
                      indeed mediated by the glutamate-grabbing activity
                      associated with EAAT2 functionality. Unexpectedly, both cell
                      doses of non-transfected MSCs induced higher protection than
                      transfected EAAT2–MSCs by another mechanism independent of
                      the glutamate-grabbing capacity.InterpretationAlthough the
                      transfection procedure most likely interferes with some of
                      the intrinsic protective mechanisms of mesenchymal cells,
                      the results show that the induced expression of EAAT2 in
                      cells represents a novel alternative to mitigate the
                      excitotoxic effects of glutamate and paves the way to
                      combine this strategy with current cell therapies for
                      cerebral ischemia.},
      cin          = {ICS-4},
      ddc          = {610},
      cid          = {I:(DE-Juel1)ICS-4-20110106},
      pnm          = {552 - Engineering Cell Function (POF3-552)},
      pid          = {G:(DE-HGF)POF3-552},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:30555045},
      UT           = {WOS:000456677400024},
      doi          = {10.1016/j.ebiom.2018.11.024},
      url          = {https://juser.fz-juelich.de/record/859963},
}