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Stem Cells Int. 2016;2016:2640746. doi: 10.1155/2016/2640746. Epub 2016 Jan 04.

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 international

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

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.

PMID: 27057168 PMCID: PMC4736319 DOI: 10.1155/2016/2640746

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.

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