Derivation of Glucose-Competent Human Pancreatic Endocrine Cells via the Generation of Interspecies Chimeras Using the Chicken Embryo as a Host
Patients with type 1 diabetes (T1D) suffer from glycose metabolic imbalance due to destruction of their glucose sensing pancreatic β-cells. β-cells can secrete insulin in response to elevated blood glucose levels and are the predominant endocrine cells in pancreatic islets. The current treatment for T1D consists of near constant surveillance of blood glucose levels and regulation via painful insulin injections. A promising, potentially curative, therapeutic approach is to transplant β-cells in T1D patients using pancreatic islets derived from donors. Unfortunately, the number of patients requiring a transplantation far exceeds the number of available donor cells. Current efforts have focused on the in vitro derivation of pancreatic islet cells through the differentiation of pluripotent stem cells or the direct reprogramming of mature cell types. However, a major challenge associated with the derivation of pancreatic islet cells is achieving recapitulation of developmental processes in vitro in order to obtain a cell product that perfectly phenocopies the endogenous cell type. Furthermore, in vitro differentiation or cell reprograming result in a heterogeneous cell population which increases the risk of teratoma formation upon transplantation. A promising alternative approach for the derivation of pancreatic islets is interspecies chimeras; a technique that relies on the developmental niche of a host embryo to differentiate multipotent human cells into fully-differentiated cells that are safe for transplantation. Our goal is to establish an experimental platform for the generation of interspecies chimera-derived autologous glucose-competent pancreatic islets.