Adhesion Molecule Function in Human Hematopoietic Development
Bone marrow transplantation provides a source for human blood stem cells. These cells have been used for years in the treatment of immunodeficiency, cancer and other genetic disorders. Unfortunately, human blood stem cells have a short life span and cannot be easily expanded in the laboratory setting. These shortcomings can be circumvented by the use of human embryonic stem cells (hESC). Human ESC can produce every tissue of the body (including blood), and can be expanded indefinitely in the laboratory. The goal of our work is to understand the cues that control hESC generation of blood cells. In particular, we want to define the role played by adhesion molecules, molecules that mediate cell-to-cell interactions, in the generation of blood cells from hESC.
To achieve our goals, we need to develop new tools that will allow us to follow the hESC as they progress down the pathway of becoming a blood cell. In particular, we propose to endow hESC with a reporter molecule that will identify cells that have decided to follow the blood cell path. Moreover, we will develop novel culture methods in the laboratory to assay the hESC’s capacity to produce blood cells. These innovative tools will permit us to determine which adhesion molecules are present in hESC and how the expression of these molecules fluctuate during the process of blood generation.
Understanding the process of blood generation from hESC will allow us to develop new therapeutic strategies for the treatment of immunodeficiency and cancer. This aspect of Regenerative Medicine will have major impacts on the way that bone marrow and blood stem cell transplantation is done, hopefully reducing or completely eliminating the detrimental side effects of this therapy.
California has been at the forefront of scientific discovery. It is known throughout this country for its cutting edge approach to scientific research. The work described in this proposal will help increase our understanding of the process of blood cell generation from human embryonic stem cells. Ultimately, this knowledge will allow us to develop new therapeutic strategies for the treatment of many diseases, including transplantation of blood stem cells to treat immunodeficiency, genetic deficiencies and cancer.
California will benefit directly from these discoveries at multiple levels. First, it will support the state reputation as a beacon of scientific discovery. This will positively influence the recruitment of students, scientists and medical doctors to the state, thereby increasing the intellectual pool that will further feed California’s scientific and intellectual engine. Second, discoveries of this nature will foster more entrepreneurial and biotechnological developments within the state, resulting in the creation of companies that will provide needed jobs and help the state’s economy. Lastly, the creation of these companies will result in the promotion of these scientific discoveries to the clinical setting, ultimately benefiting California’s citizens that desperately need these life saving therapies.