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  2. A change in the zinc ion concentration reflects the maturation of insulin-producing cells generated from adipose-derived mesenchymal stem cells

A change in the zinc ion concentration reflects the maturation of insulin-producing cells generated from adipose-derived mesenchymal stem cells

  • Sci Rep. 2019 Dec 10;9(1):18731. doi: 10.1038/s41598-019-55172-0.
Shogo Ohta 1 Tetsuya Ikemoto 2 Yuma Wada 1 Yu Saito 1 Shinichiro Yamada 1 Satoru Imura 1 Yuji Morine 1 Mitsuo Shimada 1
Affiliations

Affiliations

  • 1 Department of Digestive and Transplant Surgery, Tokushima University, 3-18-15 Kuramoto, Tokushima, 770-8503, Japan.
  • 2 Department of Digestive and Transplant Surgery, Tokushima University, 3-18-15 Kuramoto, Tokushima, 770-8503, Japan. ikemoto.tetsuya@tokushima-u.ac.jp.
Abstract

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.

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