Modeling Pancreatic Endocrine Cell Development
There remains an urgent and critical need for a cell-based cure for diabetes. Islet transplantation with persistent immune suppression has shown promise in curing T1D. However, one major obstacle towards large scale implementation of this approach is the shortage of engraftable islets. Human embryonic stem cell (hESCs), which can undergo unlimited self-renewal and differentiate into all cell types in the body, have the potential to become an unlimited source of glucose responsive, insulin producing cells that function as a de facto pancreatic β cells. Ongoing research in our laboratories is directed at developing novel strategies to derive these cells from hESCs. Although much progress has been made over the past decade to generate insulin-producing cells for replacement therapies in T1D, the most efficient protocols require manipulation of cells in a petri dish followed by transplantation and maturation within a model (animal) system. The differentiation and maturation of stem cells within the animal is often referred to as the ‘black box’ period. It is our belief that we must systematically study the ‘black box’, or unknown points in differentiation, and understand on a biochemical and genetic level the mechanisms that underlie the development of pancreatic endocrine cells. We hypothesize that targeting key points in the differentiation process will create a population of cells of significant therapeutic impact and will ultimately lead to novel treatments for T1D.