Insulin-Deficient Diabetic Condition Upregulates the Insulin-Secreting Capacity of Human Induced Pluripotent Stem Cell-Derived Pancreatic Endocrine Progenitor Cells After Implantation in Mice

• 豊田, 太郎

  T-CiRA Discovery, Takeda Pharmaceutical Company Limited･Takeda-CiRA Joint Program for iPS Cell Applications (T-CiRA)

• Ueno, Hikaru

  T-CiRA Discovery, Takeda Pharmaceutical Company Limited･Takeda-CiRA Joint Program for iPS Cell Applications (T-CiRA)

• Tsubooka-Yamazoe, Noriko

  T-CiRA Discovery, Takeda Pharmaceutical Company Limited･Takeda-CiRA Joint Program for iPS Cell Applications (T-CiRA)

• Hiyoshi, Hideyuki

  T-CiRA Discovery, Takeda Pharmaceutical Company Limited･Takeda-CiRA Joint Program for iPS Cell Applications (T-CiRA)

• Ito, Ryo

  T-CiRA Discovery, Takeda Pharmaceutical Company Limited･Takeda-CiRA Joint Program for iPS Cell Applications (T-CiRA)

• Matsumoto, Hirokazu

  Takeda-CiRA Joint Program for iPS Cell Applications (T-CiRA)･Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto University

• Toyoda, Taro

抄録

The host environment is a crucial factor for considering the transplant of stem cell–derived immature pancreatic cells in patients with type 1 diabetes. Here, we investigated the effect of insulin (INS)-deficient diabetes on the fate of immature pancreatic endocrine cell grafts and the underlying mechanisms. Human induced pluripotent stem cell–derived pancreatic endocrine progenitor cells (EPCs), which contained a high proportion of chromogranin A⁺ NK6 homeobox 1⁺ cells and very few INS⁺ cells, were used. When the EPCs were implanted under the kidney capsule in immunodeficient mice, INS-deficient diabetes accelerated increase in plasma human C-peptide, a marker of graft-derived INS secretion. The acceleration was suppressed by INS infusion but not affected by partial attenuation of hyperglycemia by dapagliflozin, an INS-independent glucose-lowering agent. Immunohistochemical analyses indicated that the grafts from diabetic mice contained more endocrine cells including proliferative INS-producing cells compared with that from nondiabetic mice, despite no difference in whole graft mass between the two groups. These data suggest that INS-deficient diabetes upregulates the INS-secreting capacity of EPC grafts by increasing the number of endocrine cells including INS-producing cells without changing the graft mass. These findings provide useful insights into postoperative diabetic care for cell therapy using stem cell–derived pancreatic cells.

収録刊行物

• Diabetes

  Diabetes 69 (4), 634-646, 2020-04

  American Diabetes Association

詳細情報

• CRID: 1050003824826393600
• NII論文ID: 120006865697
• ISSN: 00121797
• HANDLE: 2433/252365
• 本文言語コード: en
• 資料種別: journal article
• データソース種別:
  • IRDB
  • CiNii Articles