title: Cannabidiol Modulates the Immunophenotype and Inhibits the Activation of the Inflammasome in Human Gingival Mesenchymal Stem Cells.
abstract: Human Gingival Mesenchymal Stem Cells (hGMSCs) are multipotential cells that can expand and differentiate in culture under specific and standardized conditions. In the present study, we have investigated whetherin vitropre-treatment of hGMSCs with Cannabidiol (CBD) can influence their expression profile, improving the therapeutic potential of this cell culture. Following CBD treatment (5 μM) for 24 h, gene expression analysis through Next Generation Sequencing (NGS) has revealed several genes differentially expressed between CBD-treated hGMSCs (CBD-hGMSCs) and control cells (CTR-hGMSCs) that were linked to inflammation and apoptosis. In particular, we have demonstrated that CBD treatment in hGMSCs prevented the activation of the NALP3-inflammasome pathway by suppressing the levels of NALP3, CASP1, and IL18, and in parallel, inhibited apoptosis, as demonstrated by the suppression of Bax. CBD treatment was also able to modulate the expression of the well-known mesenchymal stem cell markers (CD13, CD29, CD73, CD44, CD90, and CD166), and other surface antigens. Specifically, CBD led to the downregulation of genes codifying for antigens involved in the activation of the immune system (CD109, CD151, CD40, CD46, CD59, CD68, CD81, CD82, CD99), while it led to the upregulation of those implicated in the inhibition of the immune responses (CD47, CD55, CD276). In conclusion, the present study will provide a new simple and reproducible method for preconditioning hGMSCs with CBD, before transplantation, as an interesting strategy for improving the hGMSCs molecular phenotype, reducing the risk of immune or inflammatory reactions in the host, and in parallel, for increasing their survival and thus, their long-term therapeutic efficacy.
authors.affiliation: Experimental Neurology Laboratory, IRCCS Centro Neurolesi "Bonino-Pulejo" Messina, Italy.
authors.forename: Rosaliana
authors.initials: R
authors.lastname: Libro
authors.affiliation: Experimental Neurology Laboratory, IRCCS Centro Neurolesi "Bonino-Pulejo" Messina, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Scionti
authors.affiliation: Stem Cells and Regenerative Medicine Laboratory, Department of Medical, Oral and Biotechnological Sciences, University "G. d'Annunzio" Chieti-Pescara, Chieti, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Diomede
authors.affiliation: Department of Medicine and Aging Sciences, University "G. d'Annunzio" Chieti-Pescara, Chieti, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Marchisio
authors.affiliation: Council for Research and Experimentation in Agriculture - Research Centre for Industrial Crops (CRA-CIN) Rovigo, Italy.
authors.forename: Gianpaolo
authors.initials: G
authors.lastname: Grassi
authors.affiliation: Dipartimento di Scienze del Farmaco, Università del Piemonte Orientale Novara, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Pollastro
authors.affiliation: Stem Cells and Regenerative Medicine Laboratory, Department of Medical, Oral and Biotechnological Sciences, University "G. d'Annunzio" Chieti-Pescara, Chieti, Italy.
authors.forename: Adriano
authors.initials: A
authors.lastname: Piattelli
authors.affiliation: Experimental Neurology Laboratory, IRCCS Centro Neurolesi "Bonino-Pulejo" Messina, Italy.
authors.forename: Placido
authors.initials: P
authors.lastname: Bramanti
authors.affiliation: Experimental Neurology Laboratory, IRCCS Centro Neurolesi "Bonino-Pulejo" Messina, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Mazzon
authors.affiliation: Stem Cells and Regenerative Medicine Laboratory, Department of Medical, Oral and Biotechnological Sciences, University "G. d'Annunzio" Chieti-Pescara, Chieti, Italy.
authors.forename: Oriana
authors.initials: O
authors.lastname: Trubiani
keywords: cannabidiol; human gingival mesenchymal stem cells; immunophenotype; inflammasome; next generation sequencing