Blood stem cell transplantation is an effective treatment for patients with hereditary blood cell disorders which include severe combined immunodeficiency, sickle cell disease, thalassemia, Fanconi anemia, and a possible life-saving treatment for patients of myelodysplastic syndrome, myeloid proliferative neoplasm, and various forms of leukemia. One major limitation of treating these diseases with blood cell transplantation is to find compatible donors. Blood stem cells for transplantation can be from bone marrow, specially mobilized peripheral blood, or umbilical cord blood. A major advantage of using cord blood in transplantation is a significantly lower rate of immune complication, which allows a greater degree of mismatch and results in increasing the donor pool. Furthermore, cord blood collection is simple and there is no risk to mother or infant. However, the biggest hurdle for using cord blood in transplantation is that the number of blood stem cells in a single umbilical cord is insufficient for an adult or older pediatric patient. Hence, methods to expand blood stem cells are urgently needed in the treatment of patients whose lives may be saved or quality of life may be significantly improved with transplantation. In this application, we propose to study the basic biology of using a special gene expression regulator to increase the number of donor blood stem cells in culture. This is highly relevant to the main goals of CIRM.
Statement of Benefit to California:
Thousands of Californians suffer from blood-related diseases that may potentially be cured with blood stem cell transplantation. However, these life-saving measures are limited by a lack of eligible donors. This problem is much worse for non-Caucasians, who represent a significant proportion of California’s population, due to an insufficient number of non-Caucasian donors in blood stem cell registries. Bone marrow, stimulated peripheral blood, and umbilical cord blood are three resources for transplantation. A major advantage of using cord blood is that it allows for a higher degree of immune mismatching, which would increase the number of suitable donors for blood stem cell transplantation to benefit more patients. A major issue of using cord blood is the limited stem cell number in each umbilical cord. We propose to examine a novel approach to expand the number of blood stem cells from available cord blood for transplantation. One long term benefit of the proposed work is to improve the treatment of thousands of Californian patients who need to receive healthy, functioning blood stem cells to alleviate their disease conditions. In turn, this will benefit California’s financial status in reducing the cost of treating these patients with expensive yet ineffective methods. Furthermore, the proposed research will continue to maintain California’s leadership in the field of stem cell research and provide training and education for some of California’s bright young minds.