Blood glutamate EAAT 2 -cell grabbing therapy in cerebral ischemia
Excitatory amino acid transporter 2 (EAAT ) plays a pivotal role in glutamate clearance in the adult brain, thereby preventing excitotoxic effects. Considering the high efficacy of EAAT for glutamate uptake, we hypothesized that the expression of this transporter in mesenchymal stem cells (MSCs) for...
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Published in | EBioMedicine Vol. 39; p. 118 |
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Main Authors | , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Netherlands
01.01.2019
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Abstract | Excitatory amino acid transporter 2 (EAAT
) plays a pivotal role in glutamate clearance in the adult brain, thereby preventing excitotoxic effects. Considering the high efficacy of EAAT
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.
To address this hypothesis, EAAT
-encoding cDNA was introduced into MSCs and human embryonic kidney 293 cells (HEK cells) as the control cell line. EAAT
expression and functionality were evaluated by in vitro assays. Blood glutamate-grabbing activity was tested in healthy and ischemic rat models treated with 3 × 10
and 9 × 10
cells/animal.
The expression of EAAT
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 EAAT
-HEK at low dose, confirmed that this effect was indeed mediated by the glutamate-grabbing activity associated with EAAT
functionality. Unexpectedly, both cell doses of non-transfected MSCs induced higher protection than transfected EAAT
-MSCs by another mechanism independent of the glutamate-grabbing capacity.
Although the transfection procedure most likely interferes with some of the intrinsic protective mechanisms of mesenchymal cells, the results show that the induced expression of EAAT
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. |
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AbstractList | Excitatory amino acid transporter 2 (EAAT
) plays a pivotal role in glutamate clearance in the adult brain, thereby preventing excitotoxic effects. Considering the high efficacy of EAAT
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.
To address this hypothesis, EAAT
-encoding cDNA was introduced into MSCs and human embryonic kidney 293 cells (HEK cells) as the control cell line. EAAT
expression and functionality were evaluated by in vitro assays. Blood glutamate-grabbing activity was tested in healthy and ischemic rat models treated with 3 × 10
and 9 × 10
cells/animal.
The expression of EAAT
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 EAAT
-HEK at low dose, confirmed that this effect was indeed mediated by the glutamate-grabbing activity associated with EAAT
functionality. Unexpectedly, both cell doses of non-transfected MSCs induced higher protection than transfected EAAT
-MSCs by another mechanism independent of the glutamate-grabbing capacity.
Although the transfection procedure most likely interferes with some of the intrinsic protective mechanisms of mesenchymal cells, the results show that the induced expression of EAAT
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. |
Author | da Silva-Candal, Andrés Pérez-Mato, María Fernández-Susavila, Héctor Argibay, Bárbara Pérez-Díaz, Amparo Sobrino, Tomás Correa-Paz, Clara Vieites-Prado, Alba Ávila-Gómez, Paulo Günther, Anne Iglesias-Rey, Ramón Baumann, Arnd Dopico-López, Antonio Campos, Francisco Isabel Loza, M Castillo, José |
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Keywords | Cerebral ischemia Excitotoxic protection Cell therapy Excitatory amino acid transporter 2 Excitotoxic injury Glutamate Mesenchymal stem cells |
Language | English |
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Title | Blood glutamate EAAT 2 -cell grabbing therapy in cerebral ischemia |
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