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Inhibitory Effects of iPSC-MSCs and Their Extracellular Vesicles on the Onset of Sialadenitis in a Mouse Model of Sjögren's Syndrome

No effective treatment for Sjögren's syndrome (SS), a chronic autoimmune disease affecting mainly salivary and lacrimal glands, is available now. Systemic infusion of allogeneic mesenchymal stem cells (MSCs) isolated from tissues such as bone marrow (BM) alleviated SS in mouse models and a smal...

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Autores principales: Hai, Bo, Shigemoto-Kuroda, Taeko, Zhao, Qingguo, Lee, Ryang Hwa, Liu, Fei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5875028/
https://www.ncbi.nlm.nih.gov/pubmed/29736173
http://dx.doi.org/10.1155/2018/2092315
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author Hai, Bo
Shigemoto-Kuroda, Taeko
Zhao, Qingguo
Lee, Ryang Hwa
Liu, Fei
author_facet Hai, Bo
Shigemoto-Kuroda, Taeko
Zhao, Qingguo
Lee, Ryang Hwa
Liu, Fei
author_sort Hai, Bo
collection PubMed
description No effective treatment for Sjögren's syndrome (SS), a chronic autoimmune disease affecting mainly salivary and lacrimal glands, is available now. Systemic infusion of allogeneic mesenchymal stem cells (MSCs) isolated from tissues such as bone marrow (BM) alleviated SS in mouse models and a small clinical trial, but further research and application of this MSC therapy were hindered by limited expandability, significant donor variations, and safety concerns of tissue-derived MSCs. To circumvent these issues, we derived MSCs from human iPSCs using an optimized protocol that can be easily scaled up to produce a huge amount of standardized MSCs. Our iPSC-MSCs inhibited the onset of lymphocyte infiltration into salivary glands in the NOD mouse model of SS in the same way as BM-MSCs. Extracellular vesicles (EVs) carry bioactive molecules in the same way as their originating cells and are more stable and considered much safer than cells for therapies. We found that EVs derived from BM-MSCs and iPSC-MSCs suppressed activation of immune cells and expression of proinflammation factors essential for SS progression in vitro and that infusion of iPSC-MSC EVs at the predisease stage decreased the lymphocyte infiltration in salivary glands and serum autoantibody levels in the same way as infusion of BM-MSCs and iPSC-MSCs. These data suggested that iPSC-MSC EVs have the potential to prevent the progression of SS before the onset of sialadenitis.
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spelling pubmed-58750282018-05-07 Inhibitory Effects of iPSC-MSCs and Their Extracellular Vesicles on the Onset of Sialadenitis in a Mouse Model of Sjögren's Syndrome Hai, Bo Shigemoto-Kuroda, Taeko Zhao, Qingguo Lee, Ryang Hwa Liu, Fei Stem Cells Int Research Article No effective treatment for Sjögren's syndrome (SS), a chronic autoimmune disease affecting mainly salivary and lacrimal glands, is available now. Systemic infusion of allogeneic mesenchymal stem cells (MSCs) isolated from tissues such as bone marrow (BM) alleviated SS in mouse models and a small clinical trial, but further research and application of this MSC therapy were hindered by limited expandability, significant donor variations, and safety concerns of tissue-derived MSCs. To circumvent these issues, we derived MSCs from human iPSCs using an optimized protocol that can be easily scaled up to produce a huge amount of standardized MSCs. Our iPSC-MSCs inhibited the onset of lymphocyte infiltration into salivary glands in the NOD mouse model of SS in the same way as BM-MSCs. Extracellular vesicles (EVs) carry bioactive molecules in the same way as their originating cells and are more stable and considered much safer than cells for therapies. We found that EVs derived from BM-MSCs and iPSC-MSCs suppressed activation of immune cells and expression of proinflammation factors essential for SS progression in vitro and that infusion of iPSC-MSC EVs at the predisease stage decreased the lymphocyte infiltration in salivary glands and serum autoantibody levels in the same way as infusion of BM-MSCs and iPSC-MSCs. These data suggested that iPSC-MSC EVs have the potential to prevent the progression of SS before the onset of sialadenitis. Hindawi 2018-03-15 /pmc/articles/PMC5875028/ /pubmed/29736173 http://dx.doi.org/10.1155/2018/2092315 Text en Copyright © 2018 Bo Hai et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Hai, Bo
Shigemoto-Kuroda, Taeko
Zhao, Qingguo
Lee, Ryang Hwa
Liu, Fei
Inhibitory Effects of iPSC-MSCs and Their Extracellular Vesicles on the Onset of Sialadenitis in a Mouse Model of Sjögren's Syndrome
title Inhibitory Effects of iPSC-MSCs and Their Extracellular Vesicles on the Onset of Sialadenitis in a Mouse Model of Sjögren's Syndrome
title_full Inhibitory Effects of iPSC-MSCs and Their Extracellular Vesicles on the Onset of Sialadenitis in a Mouse Model of Sjögren's Syndrome
title_fullStr Inhibitory Effects of iPSC-MSCs and Their Extracellular Vesicles on the Onset of Sialadenitis in a Mouse Model of Sjögren's Syndrome
title_full_unstemmed Inhibitory Effects of iPSC-MSCs and Their Extracellular Vesicles on the Onset of Sialadenitis in a Mouse Model of Sjögren's Syndrome
title_short Inhibitory Effects of iPSC-MSCs and Their Extracellular Vesicles on the Onset of Sialadenitis in a Mouse Model of Sjögren's Syndrome
title_sort inhibitory effects of ipsc-mscs and their extracellular vesicles on the onset of sialadenitis in a mouse model of sjögren's syndrome
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5875028/
https://www.ncbi.nlm.nih.gov/pubmed/29736173
http://dx.doi.org/10.1155/2018/2092315
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