This research project is aimed at developing improved methods to blood cell diseases such as thalassemia and sickle cell anemia by stem cell transplantation prior to birth. It is now possible to detect many inherited diseases early in pregnancy. It may also be possible to treat diseases that prevent normal stem cell function by transplantation of healthy stem cells into a fetus with a birth defect. There are potential advantages to such a therapy such as early treatment of disease and a lower risk of rejection because the immune system is not fully developed early in fetal development. This proposal aims to determine the best type of stem cells for fetal transplantation by studying the growth and differentiation properties of blood stem cells at different ages of development to determine if young stem cells are best for prenatal transplantation. This proposal will also test the role of a type of immune cell, natural killer cells, in aiding engraftment of stem cells transplanted into fetuses. These studies will result in a better understanding of the optimal type and mixture of stem cells and blood cells for prenatal transplantation.
Statement of Benefit to California:
This study is aimed at improving the method of prenatal transplantation to treat inherited birth defect that affect the normal function of blood cells. Currently this form of therapy works for some rare forms of immunodeficiency but, if the effectiveness at which healthy stem cells can be introduced to fetuses improves, many more diseases could be treated. Transplanting healthy cells offers treatment or a cure for many blood diseases such as those that affect the function of red blood cells, collectively referred to as hemoglobinopathies. These diseases affect lives of thousands of California denizens. The lack of available or suitable donor tissue prevents therapy in many cases. Prenatal transplantation offers the hope of avoiding the need for tissue matching thus allowing for treatment of the disease before birth, which may lead to a life-long cure of the disease. The successful outcome of this work will offer new hope to many future Californians and their families suffering from inherited blood cell diseases. This will improve lives and save money on long-term health care costs associated with these diseases. Development of the technologies and expertise to bring these novel forms of therapy from the laboratory bench to hospital bedside will also keep California in the forefront of the biotechnology industry, will attract talented scientists and clinicians to California and will create high-paying jobs.