Grant: Operating Grant

Human pluripotent stem cells (stem cells) have the potential to generate cells and tissues capable of treating many degenerative diseases. The clinical evaluation of stem cell-derived cells is limited by challenges in guiding their differentiation and maturation into relevant target cell types (such as blood cells), and by our inability to produce sufficient quantities of these target cells to enable clinical trials. As we have demonstrated over the last 5 years, novel technologies to engineer the environment around stem cells (so called "niches") represent powerful tools to understand fundamental mechanisms in stem cell fate control and to enable the robust generation of early stem cell derivatives. This project will take advantage of our ability to generate mesoderm (a primary developmental cell layer that gives rise to tissues such as blood and endothelial cells) to engineer artificial niches to guide the generation of adult-like blood cell progenitors from stem cells. Furthermore, we will specifically demonstrate the developmental capacity of these adult-like blood cell progenitors by guiding their differentiation into functional immune cells (T-cells) using a novel 3-D assay. This project will provide new fundamental insight into the origin of definitive human blood progenitor cells, enable the generation of these cells from a renewable source of stem cells, and lay the foundation for the use of these cells to model immune diseases.