Pharmacological Inhibition of Gal-3 in Mesenchymal Stem Cells Enhances Their Capacity to Promote Alternative Activation of Macrophages in Dextran Sulphate Sodium-Induced Colitis

Bojana Simovic Markovic; Aleksandar Nikolic; Marina Gazdic; Jasmin Nurkovic; Irena Djordjevic; Nebojsa Arsenijevic; Miodrag Stojkovic; Miodrag L Lukic; Vladislav Volarevic

doi:10.1155/2016/2640746

Pharmacological Inhibition of Gal-3 in Mesenchymal Stem Cells Enhances Their Capacity to Promote Alternative Activation of Macrophages in Dextran Sulphate Sodium-Induced Colitis

Stem Cells Int. 2016:2016:2640746. doi: 10.1155/2016/2640746. Epub 2016 Jan 4.

Authors

Bojana Simovic Markovic¹, Aleksandar Nikolic¹, Marina Gazdic¹, Jasmin Nurkovic², Irena Djordjevic¹, Nebojsa Arsenijevic¹, Miodrag Stojkovic³, Miodrag L Lukic¹, Vladislav Volarevic¹

Affiliations

¹ Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, 69 Svetozar Markovic Street, 34000 Kragujevac, Serbia.
² Stem Cell Laboratory, Department of Biomedical Sciences, State University of Novi Pazar, Nn Vuk Karadzic Street, 36300 Novi Pazar, Serbia.
³ Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, 69 Svetozar Markovic Street, 34000 Kragujevac, Serbia; Spebo Medical, 16 Norvezanska Street, 16000 Leskovac, Serbia.

Abstract

Transplantation of mesenchymal stem cells (MSCs) reduces the severity of dextran sulphate sodium- (DSS-) induced colitis. MSCs are able to secrete Galectin-3 (Gal-3), a protein known to affect proliferation, adhesion, and migration of immune cells. We investigate whether newly synthetized inhibitor of Gal-3 (Davanat) will affect production of Gal-3 in MSCs and enhance their potential to attenuate DSS-induced colitis. Pharmacological inhibition of Gal-3 in MSCs enhances their capacity to promote alternative activation of peritoneal macrophages in vitro and in vivo. Injection of MSCs cultured in the presence of Davanat increased concentration of IL-10 in sera of DSS-treated animals and markedly enhanced presence of alternatively activated and IL-10 producing macrophages in the colons of DSS-treated mice. Pharmacological inhibition of Gal-3 in MSCs significantly attenuates concentration of Gal-3 in sera of DSS-treated animals, indicating that MSCs produce Gal-3 in this disease. In conclusion, our findings indicate that Davanat could be used for improvement of MSC-mediated polarization towards immunosuppressive M2 phenotype of macrophages.