Hematopoietic stem cell transplantation provides a life-saving treatment for individuals who have certain genetic abnormalities affecting their hematopoietic system, or for individuals treated for malignant diseases such as leukemia. However, some individuals are unable to receive this life saving treatment due to the inability to find a suitably matched hematopoietic stem cell donor. While umbilical cord blood may alleviate some of those issues, there are still concerns associated with cost and complexity. Previous studies have identified that human embryonic stem cells are able to differentiate into hematopoietic stem cells in the laboratory research setting. While these cells are able to resemble hematopoietic stem cells, very little success has been met regarding the ability of the cells to functionally engraft in the bone marrow using methodologies similar to that used for bone marrow transplantation purposes. Previously we have elucidated some of the key regulators involved in the multiple steps of hematopoietic stem cell engraftment. We aim to use this knowledge to define optimal conditions that allow for the differentiation of human embryonic stem cells into hematopoietic stem cells that are able to function in settings of bone marrow transplantation. This will involve identification of the molecules known to be involved in the multiple coordinated steps of hematopoietic stem cell engraftment and the manipulation of the cells to allow for efficient expression. It is anticipated that these studies will allow for identification of the methods for efficient differentiation of in vivo functional hematopoietic stem cells that can be used in clinical settings of bone marrow transplantation.
Statement of Benefit to California:
While hematopoietic stem cell transplantation provides a life-saving treatment for many individuals, in ethnically diverse states such as California, fewer individuals are unable to find suitable donors than in less ethnically diverse regions due to biases in the unrelated marrow donor registries. Therefore, alternatives need to be developed which are able to eliminate these issues. One such approach for hematopoietic stem cell transplantation is to derive the stem cells from a range of human embryonic stem cells so that all patients will be equally able to find matched donor cells. However, the efficient differentiation protocols to achieve this have yet to be defined. Using our knowledge of the mechanisms of hematopoietic stem cell engraftment, we aim to define methods that allow for the differentiation of functional hematopoietic stem cells. This may ultimately allow for the routine use of this potentially limitless supply of cells in the clinical need of bone marrow transplantation.