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Syngeneically transplanted insulin producing cells differentiated from adipose derived stem cells undergo delayed damage by autoimmune responses in NOD mice
Insulin-producing cells (IPCs) generated by our established protocol have reached the non-clinical ‘proof of concept’ stage. Our strategy for their clinical application is the autotransplantation of IPCs into patients with type 1 diabetes mellitus (T1DM). In this context, the autoimmunity that chara...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8991208/ https://www.ncbi.nlm.nih.gov/pubmed/35393479 http://dx.doi.org/10.1038/s41598-022-09838-x |
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author | Tokuda, Kazunori Ikemoto, Tetsuya Yamashita, Shoko Miyazaki, Katsuki Okikawa, Shohei Yamada, Shinichiro Saito, Yu Morine, Yuji Shimada, Mitsuo |
author_facet | Tokuda, Kazunori Ikemoto, Tetsuya Yamashita, Shoko Miyazaki, Katsuki Okikawa, Shohei Yamada, Shinichiro Saito, Yu Morine, Yuji Shimada, Mitsuo |
author_sort | Tokuda, Kazunori |
collection | PubMed |
description | Insulin-producing cells (IPCs) generated by our established protocol have reached the non-clinical ‘proof of concept’ stage. Our strategy for their clinical application is the autotransplantation of IPCs into patients with type 1 diabetes mellitus (T1DM). In this context, the autoimmunity that characterized T1DM is important, rather than allorejection. We aimed to determine how these IPCs respond to T1DM autoimmunity. IPCs were generated from the subcutaneous fat tissue of non-obese diabetic (NOD) mice using our protocol. IPCs derived from NOD mice were transplanted under the kidney capsules of NOD mice at the onset of diabetes and the subsequent changes in blood glucose concentration were characterized. Blood glucose decreased within 30 days of transplantation, but increased again after 40–60 days in three of four recipient NOD mice. In tissue samples, the numbers of CD4(+) and CD8(+) T cells were significantly higher 60 days after transplantation than 30 days after transplantation. In conclusion, IPCs significantly ameliorate the diabetes of mice in the short term, but are damaged by autoimmunity in the longer term, as evidenced by local T cells accumulation. This study provides new insights into potential stem cell therapies for T1DM. |
format | Online Article Text |
id | pubmed-8991208 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-89912082022-04-11 Syngeneically transplanted insulin producing cells differentiated from adipose derived stem cells undergo delayed damage by autoimmune responses in NOD mice Tokuda, Kazunori Ikemoto, Tetsuya Yamashita, Shoko Miyazaki, Katsuki Okikawa, Shohei Yamada, Shinichiro Saito, Yu Morine, Yuji Shimada, Mitsuo Sci Rep Article Insulin-producing cells (IPCs) generated by our established protocol have reached the non-clinical ‘proof of concept’ stage. Our strategy for their clinical application is the autotransplantation of IPCs into patients with type 1 diabetes mellitus (T1DM). In this context, the autoimmunity that characterized T1DM is important, rather than allorejection. We aimed to determine how these IPCs respond to T1DM autoimmunity. IPCs were generated from the subcutaneous fat tissue of non-obese diabetic (NOD) mice using our protocol. IPCs derived from NOD mice were transplanted under the kidney capsules of NOD mice at the onset of diabetes and the subsequent changes in blood glucose concentration were characterized. Blood glucose decreased within 30 days of transplantation, but increased again after 40–60 days in three of four recipient NOD mice. In tissue samples, the numbers of CD4(+) and CD8(+) T cells were significantly higher 60 days after transplantation than 30 days after transplantation. In conclusion, IPCs significantly ameliorate the diabetes of mice in the short term, but are damaged by autoimmunity in the longer term, as evidenced by local T cells accumulation. This study provides new insights into potential stem cell therapies for T1DM. Nature Publishing Group UK 2022-04-07 /pmc/articles/PMC8991208/ /pubmed/35393479 http://dx.doi.org/10.1038/s41598-022-09838-x Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Tokuda, Kazunori Ikemoto, Tetsuya Yamashita, Shoko Miyazaki, Katsuki Okikawa, Shohei Yamada, Shinichiro Saito, Yu Morine, Yuji Shimada, Mitsuo Syngeneically transplanted insulin producing cells differentiated from adipose derived stem cells undergo delayed damage by autoimmune responses in NOD mice |
title | Syngeneically transplanted insulin producing cells differentiated from adipose derived stem cells undergo delayed damage by autoimmune responses in NOD mice |
title_full | Syngeneically transplanted insulin producing cells differentiated from adipose derived stem cells undergo delayed damage by autoimmune responses in NOD mice |
title_fullStr | Syngeneically transplanted insulin producing cells differentiated from adipose derived stem cells undergo delayed damage by autoimmune responses in NOD mice |
title_full_unstemmed | Syngeneically transplanted insulin producing cells differentiated from adipose derived stem cells undergo delayed damage by autoimmune responses in NOD mice |
title_short | Syngeneically transplanted insulin producing cells differentiated from adipose derived stem cells undergo delayed damage by autoimmune responses in NOD mice |
title_sort | syngeneically transplanted insulin producing cells differentiated from adipose derived stem cells undergo delayed damage by autoimmune responses in nod mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8991208/ https://www.ncbi.nlm.nih.gov/pubmed/35393479 http://dx.doi.org/10.1038/s41598-022-09838-x |
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