No abstract

FDA approved Clinical Trials are already under way using stem cell-derived insulin-producing cells (IPCs) for the treatment of type 1 diabetes in humans. Differentiation methods used to derive beta-cell like IPCs have greatly improved over the last few years, resulting in highly efficacious treatment of high blood glucose in diabetic animals models. However, there still remains major challenges of developing an effective cure in humans due to challenges of delivery and long term survival and function of grafts. Like humans, spontaneous canine diabetes is a commonly diagnosed, multifactorial endocrine disorder in dogs which clinically presents as a type 1 diabetes disorder. In order to develop successful human diabetes therapies using stem cells, spontaneous canine diabetes offers a very attractive translational model. Dogs have major similarities to humans including the clinical signs, pathophysiology and long-term clinical management of the disease by use of exogenous insulin injections. Using cadaveric canine islets and our Core-Shell Spherification (CSS) microencapsulation methods, we have successfully reversed hyperglycemia in dogs for varying time periods. Our data confirms that similar to humans, islet transplantation is a viable option for diabetes treatment in dogs. To further develop canine diabetes as a translational model for human diabetes, while developing stem cell therapies for dogs, we have successfully generated IPCs from human pluripotent stem cells. The IPC clusters express key beta-cell biomarkers including PDX1, NK6.1, NeuroD1, and insulin. The majority of endocrine cells in clusters are single hormonal where separate cells express ARX and glucagon. These cell clusters corrected induced diabetes in mouse models when transplanted under the kidney capsule. Our studies will further allow us to further test the use of the canine model, both in allo- and xenogeneic transplant environments, for further pre-clinical development in humans. Disclosure A. Wildey: None. S.J. Williams: None. M. Hamilton: None. S. Harrington: None. L. Ott: Employee; Self; Likarda, LLC. F. Karanu: Employee; Self; Likarda, LLC.

No abstract