Year 3

It is well recognized from adult stem cell studies that the growth of transplanted bone marrow is generated from the hematopoietic (“blood-forming”) stem and progenitor cells provided by the donor bone marrow. Mature, differentiated cells that accompany the hematopoietic stem cells, disappear rapidly after transplantation as they lack the ability to self-renew. It is thus essential when designing clinical approaches that use tissue derived from human embryonic stem cells (hESC), to specifically target the production of stem and progenitors that will survive, proliferate and differentiate normally after transplantation. We and others have shown that blood cells can be generated from hESC. However, it has become apparent more recently that the types of blood cells that hESC can produce under current conditions are more limited functionally than those found in bone marrow or cord blood. Over the past year of funding, we have studied this problem in the following ways. First, we have identified some of the key genetic differences in the way blood is formed from hESC that may be particularly important in the formation of the lymphoid cells of the immune system. Second, we have carefully compared the hematopoietic capacity of six new embryonic stem cell lines developed at UCLA, to identify which are the best for blood formation. This work has been conducted as part of a collaboration with several teams at UCLA. Third, we have developed a way to give a signal to cord blood stem cells that induces them to make large numbers of red blood cells. We are using this same method now to stimulate red blood cell production from hESC. The ultimate goals of these studies is to improve production of hematopoietic cells from hESC for use in transplantation.