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ID 114940
Title Alternative
亜鉛イオン濃度変化は脂肪由来幹細胞から作成するインスリン産生細胞の成熟を反映する
Author
Ohta, Shogo Tokushima University
Wada, Yuma Tokushima University
Keywords
Insulin producing cell (IPC)
adipose derived stem cell (ADSC)
zinc ion (Zn)
maturation
differentiation
Content Type
Thesis or Dissertation
Description
The generation of insulin-producing cells (IPCs) from pluripotent stem cells could be a breakthrough treatment for type 1 diabetes. However, development of new techniques is needed to exclude immature cells for clinical application. Dithizone staining is used to evaluate IPCs by detecting zinc. We hypothesised that zinc ion (Zn2+) dynamics reflect the IPC maturation status. Human adipose-derived stem cells were differentiated into IPCs by our two-step protocol using two-dimensional (2D) or 3D culture. The stimulation indexes of 2D -and 3D-cultured IPCs on day 21 were 1.21 and 3.64 (P < 0.05), respectively. The 3D-cultured IPCs were stained with dithizone during culture, and its intensity calculated by ImageJ reached the peak on day 17 (P < 0.05). Blood glucose levels of streptozotocin-induced diabetic nude mice were normalised (4/4,100%) after transplantation of 96 3D-cultured IPCs. Zn2+ concentration changes in the medium of 3D cultures had a negative value in the early period and a large positive value in the latter period. This study suggests that Zn2+ dynamics based on our observations and staining of zinc transporters have critical roles in the differentiation of IPCs, and that their measurement might be useful to evaluate IPC maturation as a non-destructive method.
Journal Title
Scientific Reports
ISSN
20452322
Publisher
Springer Nature
Volume
9
Start Page
18731
Published Date
2019-12-10
Remark
内容要旨・審査要旨・論文本文の公開
本論文は, 著者Shogo Ohta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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第3428号
Diploma Number
甲医第1458号
Granted Date
2020-06-25
Degree Name
Doctor of Medical Science
Grantor
Tokushima University
departments
University Hospital
Medical Sciences