A Co-authored Paper regarding Immunocompromised type 1 Diabetic Mini-pigs was Published in the Cell Transplantation

2024.10.21

Xenogenic Engraftment of Human Induced Pluripotent Stem Cell–Derived Pancreatic Islet Cells in an Immunosuppressive Diabetic Göttingen Mini-pig Model 

Publication

Transplantation of islet-like cells generated from human pluripotent stem cells such as ES cells and iPS cells is expected to be a promising treatment for type 1 diabetes mellitus. Human iPS cell-derived pancreatic islet cells (iPIC) were discovered in a joint research project (T-CiRA) between the Center for iPS Cell Research and Application (CiRA) of Kyoto University and Takeda Pharmaceutical Company Limited. In the development of cell therapy products, it is said to be desirable to evaluate their efficacy in large animals with closer in size to humans as a bridge to clinical trials. In this paper, we induced hyperglycemia by administering streptozotocin, a drug that destroys pancreatic beta cells, to mini-pigs that underwent thymectomy and splenectomy. Furthermore, by administering immunosuppressants, we generated immunocompromised type 1 diabetic mini pigs that can be transplanted with human cells. Five weeks after implantation, histological analysis of the implanted iPICs embedded in fibrin gel revealed numerous islet-like structures with insulin-positive cells. It was also found that human C-peptide, an index of insulin secretion, was secreted into the blood. These data support the observation that the iPICs engrafted well. Future evaluation of human cells in this immunocompromised pig model could accelerate and development of cell therapy products.
In this study, Axcelead DDP was conducted the setting the target plasma levels of immunosuppressants from in vitro studies, the establishment of an immunocompromised diabetic pig model, and cell transplantation.

Axcelead DDP Solution
The advanced level of animal experimental skills of Axcelead DDP enabled to generate type 1 diabetic mini-pigs, which is difficult to maintain a stable disease state, with an immunocompromised state in which human cells are engrafted by the removal of immune system organs and the administration of immunosuppressants. Another our strength is its ability to conduct animal experiments after setting appropriate immunosuppressant doses from in vitro studies using lymphocytes. If you are in need of assistance with dosage and dosing regimens for in vivo studies, or if you are considering establishing large/small animal disease models or evaluation systems, please contact Axcelead DDP.

Related Resouces:
Center for iPS Cell Research and Application (CiRA)