| First Author | Mochida T | Year | 2020 |
| Journal | Diabetes | Volume | 69 |
| Issue | 4 | Pages | 634-646 |
| PubMed ID | 32005704 | Mgi Jnum | J:287303 |
| Mgi Id | MGI:6405654 | Doi | 10.2337/db19-0728 |
| Citation | Mochida T, et al. (2020) Insulin-Deficient Diabetic Condition Upregulates the Insulin-Secreting Capacity of Human Induced Pluripotent Stem Cell-Derived Pancreatic Endocrine Progenitor Cells After Implantation in Mice. Diabetes 69(4):634-646 |
| abstractText | 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. |
