Adipose Tissue-Derived Mesenchymal Stem Cells Exert In Vitro Immunomodulatory and Beta Cell Protective Functions in Streptozotocin-Induced Diabetic Mice Model

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 stre...

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Main Authors: Hossein Rahavi, Seyed Mahmoud Hashemi, Masoud Soleimani, Jamal Mohammadi, Nader Tajik
Format: Article
Language:English
Published: Wiley 2015-01-01
Series:Journal of Diabetes Research
Online Access:http://dx.doi.org/10.1155/2015/878535
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author Hossein Rahavi
Seyed Mahmoud Hashemi
Masoud Soleimani
Jamal Mohammadi
Nader Tajik
author_facet Hossein Rahavi
Seyed Mahmoud Hashemi
Masoud Soleimani
Jamal Mohammadi
Nader Tajik
author_sort Hossein Rahavi
collection DOAJ
description 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.
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spelling doaj-art-2f42d9d39d3e4734af44e564d74ef8392025-02-03T01:32:09ZengWileyJournal of Diabetes Research2314-67452314-67532015-01-01201510.1155/2015/878535878535Adipose Tissue-Derived Mesenchymal Stem Cells Exert In Vitro Immunomodulatory and Beta Cell Protective Functions in Streptozotocin-Induced Diabetic Mice ModelHossein Rahavi0Seyed Mahmoud Hashemi1Masoud Soleimani2Jamal Mohammadi3Nader Tajik4Division of Transplant Immunology and Immunogenetics, Immunology Research Center (IRC), Iran University of Medical Sciences, Tehran, IranDepartment of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, IranDepartment of Hematology, School of Medical Sciences, Tarbiat Modares University, Tehran, IranDivision of Transplant Immunology and Immunogenetics, Immunology Research Center (IRC), Iran University of Medical Sciences, Tehran, IranDivision of Transplant Immunology and Immunogenetics, Immunology Research Center (IRC), Iran University of Medical Sciences, Tehran, IranRegenerative 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.http://dx.doi.org/10.1155/2015/878535
spellingShingle Hossein Rahavi
Seyed Mahmoud Hashemi
Masoud Soleimani
Jamal Mohammadi
Nader Tajik
Adipose Tissue-Derived Mesenchymal Stem Cells Exert In Vitro Immunomodulatory and Beta Cell Protective Functions in Streptozotocin-Induced Diabetic Mice Model
Journal of Diabetes Research
title Adipose Tissue-Derived Mesenchymal Stem Cells Exert In Vitro Immunomodulatory and Beta Cell Protective Functions in Streptozotocin-Induced Diabetic Mice Model
title_full Adipose Tissue-Derived Mesenchymal Stem Cells Exert In Vitro Immunomodulatory and Beta Cell Protective Functions in Streptozotocin-Induced Diabetic Mice Model
title_fullStr Adipose Tissue-Derived Mesenchymal Stem Cells Exert In Vitro Immunomodulatory and Beta Cell Protective Functions in Streptozotocin-Induced Diabetic Mice Model
title_full_unstemmed Adipose Tissue-Derived Mesenchymal Stem Cells Exert In Vitro Immunomodulatory and Beta Cell Protective Functions in Streptozotocin-Induced Diabetic Mice Model
title_short Adipose Tissue-Derived Mesenchymal Stem Cells Exert In Vitro Immunomodulatory and Beta Cell Protective Functions in Streptozotocin-Induced Diabetic Mice Model
title_sort adipose tissue derived mesenchymal stem cells exert in vitro immunomodulatory and beta cell protective functions in streptozotocin induced diabetic mice model
url http://dx.doi.org/10.1155/2015/878535
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