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ID 117618
Title Alternative
同系移植された脂肪由来幹細胞から分化したインスリン産生細胞は、NODマウスの自己免疫反応により遅発性の損傷を受ける
Author
Tokuda, Kazunori Tokushima University
Miyazaki, Katsuki Tokushima University
Okikawa, Shohei Tokushima University
Keywords
insulin producing cell (IPC)
65-kDa isoform of glutamic acid decarboxylase (GAD65)
programmed cell death ligand 1 (PD-L1)
type 1 diabetes mellitus
non-obese diabetic mouse
Content Type
Thesis or Dissertation
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.
Journal Title
Scientific Reports
ISSN
20452322
Publisher
Springer Nature
Volume
12
Start Page
5852
Published Date
2022-04-07
Remark
内容要旨・審査要旨・論文本文の公開
本論文は,著者Kazunori Tokudaの学位論文として提出され,学位審査・授与の対象となっている。
Rights
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/
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第3663号
Diploma Number
甲医第1545号
Granted Date
2022-09-22
Degree Name
Doctor of Medical Science
Grantor
Tokushima University
departments
University Hospital
Medical Sciences