title: Adipose tissue-derived mesenchymal stem cells exert in vitro immunomodulatory and beta cell protective functions in streptozotocin-induced diabetic mice model.
abstract: Regenerative and immunomodulatory properties of mesenchymal stem cells (MSCs) might be applied for type 1 diabetes mellitus (T1DM) treatment. Thus, we proposed in vitro assessment of adipose tissue-derived MSCs (AT-MSCs) immunomodulation on autoimmune response along with beta cell protection in streptozotocin- (STZ-) induced diabetic C57BL/6 mice model. MSCs were extracted from abdominal adipose tissue of normal mice and cultured to proliferate. Diabetic mice were prepared by administration of multiple low-doses of streptozotocin. Pancreatic islets were isolated from normal mice and splenocytes prepared from normal and diabetic mice. Proliferation, cytokine production, and insulin secretion assays were performed in coculture experiments. AT-MSCs inhibited splenocytes proliferative response to specific (islet lysate) and nonspecific (PHA) triggers in a dose-dependent manner (P < 0.05). Decreased production of proinflammatory cytokines, such as IFN-γ, IL-2, and IL-17, and increased secretion of regulatory cytokines such as TGF-β, IL-4, IL-10, and IL-13 by stimulated splenocytes were also shown in response to islet lysate or PHA stimulants (P < 0.05). Finally, we demonstrated that AT-MSCs could effectively sustain viability as well as insulin secretion potential of pancreatic islets in the presence of reactive splenocytes (P < 0.05). In conclusion, it seems that MSCs may provide a new horizon for T1DM cell therapy and islet transplantation in the future.
authors.affiliation: Division of Transplant Immunology and Immunogenetics, Immunology Research Center (IRC), Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Hossein
authors.initials: H
authors.lastname: Rahavi
authors.affiliation: Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran ; Department of Stem Cell Biology, Stem Cell Technology Research Center, Tehran, Iran.
authors.forename: Seyed Mahmoud
authors.initials: SM
authors.lastname: Hashemi
authors.affiliation: Department of Hematology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Masoud
authors.initials: M
authors.lastname: Soleimani
authors.affiliation: Division of Transplant Immunology and Immunogenetics, Immunology Research Center (IRC), Iran University of Medical Sciences, Tehran, Iran ; Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Jamal
authors.initials: J
authors.lastname: Mohammadi
authors.affiliation: Division of Transplant Immunology and Immunogenetics, Immunology Research Center (IRC), Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Nader
authors.initials: N
authors.lastname: Tajik
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000473:pathology*; D000818:Animals; D019070:Cell Lineage; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000378:metabolism*; D005260:Female; D016130:Immunophenotyping; D007249:Inflammation; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D007515:Islets of Langerhans / Q000378:metabolism; D016381:Islets of Langerhans Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000166:cytology; D013311:Streptozocin
chemical_list: D016207:Cytokines; D007328:Insulin; D013311:Streptozocin