Contributions
Abstract: EP1457
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - 13 Experimental models
Background: Mesenchymal stem cells (MSCs) are promising candidates for MS therapies due to their anti-inflammatory properties. Although little is known about endocannabinoid system in MSCs, it has been described that Cannabidiol (CBD), a non-psychotropic cannabinoid, might enhance the therapeutic effect of these cells.
Objectives: To explore the influence of CBD in MSCs cultures as well as to test the ability of CBD to improve MSCs therapeutic effect in adoptively transferred EAE (at-EAE).
Methods: At-EAE was induced in C57BL6 mice by inoculation of encephalitogenic cells. Treatment consisted in 0.5x106 bone marrow MSCs infused twice a week. Cell infiltration, axonal loss and demyelination were analyzed ex vivo by confocal microscopy in lumbar spinal cords.
In vitro, cannabinoid receptors were determined in MSCs and encephalitogenic cells by confocal microscopy and flow cytometry. Toxicity and cytokines production mediated by CBD in co-cultures of MSCs and encephalitogenic cells were revealed by MTT and ELISA respectively. Influence of CBD in capacity of differentiation and migration of MSCs was also evaluated. Additionally, clinical parameters in at-EAE animals treated with MSCs in combination with CBD (50mg/kg/d) were studied.
Results: MSCs treatment ameliorated clinical signs of at-EAE accompanied by a reduction of cell infiltration and axonal damage. In vitro, CB1, CB2 and GPR55 receptors analysis revealed a scarce surface expression in MSCs compared to encephalitogenic cells. Furthermore, MSCs and encephalitogenic cell co-cultures, showed a reduced viability of encephalitogenic cells, a reduction in IFN-gamma and GM-CSF and an increase in CXCL-10 and IL-6 cytokines.
Addition of CBD in co-cultures resulted in a decrease in IL-6 production and adipogenic differentiation whereas migratory capacity was not modified in MSCs.
CBD concomitant treatment with MSCs cells caused a higher trend to reduce clinical signs in at-EAE compared to MSCs-treated group.
Conclusions: MSCs reduced clinical signs in vivo, diminishing neuro-inflammation and infiltration in at-EAE, concurrently with a modulation in viability and cytokines production in encephalitogenic cells in vitro. The CBD influence in IL-6 cytokine production might be related to the therapeutic effect showed in the concomitant in vivo treatment. The beneficial effect of the combination of CBD and cellular therapy opens new possibilities for the treatment of neurodegenerative disorders.
Disclosure:
Coral González García: nothing to disclosure
Ruth García Hernández: nothing to disclosure
Irene Moreno Torres: nothing to disclosure
Lucía Campos Ruíz: nothing to disclosure
María José Coronado Albí: nothing to disclosure
Arantxa García Grande: nothing to disclosure
Antonio García-Merino: has received compensation for travel expenses, speaking honoraria and consultation fees from Bayer, Merck, Teva, Biogen Idec, Novartis, Roche, Almirall, Sanofi-Aventis and Genzyme
Antonio Sánchez López: nothing to disclosure
Abstract: EP1457
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - 13 Experimental models
Background: Mesenchymal stem cells (MSCs) are promising candidates for MS therapies due to their anti-inflammatory properties. Although little is known about endocannabinoid system in MSCs, it has been described that Cannabidiol (CBD), a non-psychotropic cannabinoid, might enhance the therapeutic effect of these cells.
Objectives: To explore the influence of CBD in MSCs cultures as well as to test the ability of CBD to improve MSCs therapeutic effect in adoptively transferred EAE (at-EAE).
Methods: At-EAE was induced in C57BL6 mice by inoculation of encephalitogenic cells. Treatment consisted in 0.5x106 bone marrow MSCs infused twice a week. Cell infiltration, axonal loss and demyelination were analyzed ex vivo by confocal microscopy in lumbar spinal cords.
In vitro, cannabinoid receptors were determined in MSCs and encephalitogenic cells by confocal microscopy and flow cytometry. Toxicity and cytokines production mediated by CBD in co-cultures of MSCs and encephalitogenic cells were revealed by MTT and ELISA respectively. Influence of CBD in capacity of differentiation and migration of MSCs was also evaluated. Additionally, clinical parameters in at-EAE animals treated with MSCs in combination with CBD (50mg/kg/d) were studied.
Results: MSCs treatment ameliorated clinical signs of at-EAE accompanied by a reduction of cell infiltration and axonal damage. In vitro, CB1, CB2 and GPR55 receptors analysis revealed a scarce surface expression in MSCs compared to encephalitogenic cells. Furthermore, MSCs and encephalitogenic cell co-cultures, showed a reduced viability of encephalitogenic cells, a reduction in IFN-gamma and GM-CSF and an increase in CXCL-10 and IL-6 cytokines.
Addition of CBD in co-cultures resulted in a decrease in IL-6 production and adipogenic differentiation whereas migratory capacity was not modified in MSCs.
CBD concomitant treatment with MSCs cells caused a higher trend to reduce clinical signs in at-EAE compared to MSCs-treated group.
Conclusions: MSCs reduced clinical signs in vivo, diminishing neuro-inflammation and infiltration in at-EAE, concurrently with a modulation in viability and cytokines production in encephalitogenic cells in vitro. The CBD influence in IL-6 cytokine production might be related to the therapeutic effect showed in the concomitant in vivo treatment. The beneficial effect of the combination of CBD and cellular therapy opens new possibilities for the treatment of neurodegenerative disorders.
Disclosure:
Coral González García: nothing to disclosure
Ruth García Hernández: nothing to disclosure
Irene Moreno Torres: nothing to disclosure
Lucía Campos Ruíz: nothing to disclosure
María José Coronado Albí: nothing to disclosure
Arantxa García Grande: nothing to disclosure
Antonio García-Merino: has received compensation for travel expenses, speaking honoraria and consultation fees from Bayer, Merck, Teva, Biogen Idec, Novartis, Roche, Almirall, Sanofi-Aventis and Genzyme
Antonio Sánchez López: nothing to disclosure