Children born with sickle cell anemia and thalassemia, caused by defects in genes that make hemoglobin, may have severe anemia as well damage to virtually all the body organs: the damage begins in infancy, and is frequently fatal by early adulthood. These are the most common inherited diseases in the world: because of California’s ethnic diversity they are relatively common here, particularly in underserved populations. Our research program is dedicated to the treatment and, when possible, cure of these devastating diseases. We and others have shown that transplantation of blood stem cells from bone marrow can cure sickle cell anemia and thalassemia, and this type of stem cell therapy also has promise for treating other blood and genetic diseases. Unfortunately, not all individuals are cured after bone marrow transplantation, as this is a risky treatment. We have carried out pioneering work showing that blood from the umbilical cord (“cord blood”) of a newborn sibling can be used to cure blood disease in the affected sibling. As part of this work, we developed a program in which cord blood from newborn siblings of children with blood disease or cancer is collected and stored for later use, and large numbers of children have been cured using cord blood from this program. A significant part of our effort is devoted to discovering ways to improve and extend the use of cord blood for blood cell transplantation and make this treatment less risky. Most recently, we have found that the placenta itself is a rich source of blood stem cells, and possibly also of stem cells for tissues other than blood. We have developed a program of clinical research that is closely associated and integrated with lab research that supports investigations into ways to improve stem cell transplantation and make it available to more people. We now propose to use support from CIRM to develop a laboratory facility that will provide space for clinical and preclinical research dedicated to the improvement of blood stem cell transplantation using cord blood and placental stem cells. This facility will be used to collect, process, and freeze cord blood, and to release it for transplantation as part of the clinical research discussed above. We will explore new methods to increase yields of cord blood stem cells after collection, so that cord blood transplantation can be made available to a broader population of recipients. We will also use the facility to investigate and develop the use of placentally derived blood stem cells in transplantation, which may in the next few years result in the extension of this type of therapy to many more individuals who currently need it but do not have suitable stem cells available. This facility will thus improve and extend the use of blood stem cell transplantation for genetic diseases in California, and contribute significantly to CIRM’s goal of providing new cures for human disease.
Statement of Benefit to California:
The inherited blood diseases sickle cell anemia and thalassemia afflict significant number of individuals in California, particularly in underserved populations; both require expensive treatment during the life of the patient, and cause severe tissue damage that degrades quality of life and is often fatal. Individuals afflicted with these diseases can be cured by transplantation of blood stem cells. Nevertheless the application of this treatment is limited because the supply of donated bone marrow stem cells is limited, and because it is necessary to match certain characteristics of the donor’s and host’s immune systems. We have carried out pioneering studies demonstrating that umbilical cord blood can be used as a source of cells to cure these genetic diseases, and in some respects is superior to blood stem cells derived from bone marrow. As part of this program we have developed a program that collects, processes, stores, and distributes cord blood cells for use in transplantation. Most recently we have found that the placenta may be a source of much larger numbers of blood stem cells. We propose to develop a lab facility that will support the enlargement and extension of these investigations. We will use the facility to carry out research dedicated to the improvement of methods that use cord blood for blood stem cell transplantation, and to investigate the use of placental cells in place of cord blood. This facility will combine investigations of methods that directly support transplantation studies, and other investigations that may produce advances that will allow many more people to receive this curative therapy. In the course of this research, individuals with inherited blood diseases will receive transplants, and our extensive experience indicates these will be curative in the large majority of cases. The enhanced and extended lives of these individuals will represent a direct benefit; the savings to the health care system as a consequence of their cure is less direct but will benefit all California taxpayers. Ultimately the knowledge and experience produced by the work in the proposed facility will contribute to the goal of making blood stem cell transplantation available to a much broader group of patients, thus greatly extending the benefits to the affected individuals and to the taxpayers of California.