The overall goal of this proposal is continuation of our studies of the availability and suitability of embryonic tissue for transplantation research and therapy. In this application we focus on development and assessment of protocols for the collection, processing, cryopreservation and characterization of hematopoietic stem cells derived from embryonic human liver. Detailed study will compare functional characteristics and growth potential of these cells with data from stem cells conventionally prepared from adult bone marrow. Particular effort will also be devoted to analysis of the donor population with respect to willingness to donate conceptal tissues and incidence of risk factors for disease transmission, and to assessment of whether donated conceptal tissues meet rigorous quality standards developed by the American Association of Tissue Banks (AATB) for other transplanted tissues. Derivation of hematopoietic stem cells from embryonic liver could represent a major development in oncology as well as in the therapy of hematologic disorders; including treatment for radiation-induced aplasia. Hematopoietic stem cell transplantation, generally now, autologous, is already in widespread use in cancer chemotherapy. Transplantation of fetal hematopoietic stem cells has been shown to result in complete reconstitution of some patients with severe combined immunodeficiency disease and to improvement of individuals with a variety of other disorders like aplastic anemia, leukemia, and metabolic or storage disorders, like Gaucher's Disease. The use of embryonic liver is strongly favored because of the high relative percentage of hematopoietic stem cells compared to adult marrow and the low percentage of T-cells which reduces the risk of graft versus host reactions that occur in adult marrow transplantation. Embryonic liver cells may also be superior targets for somatic gene therapy. The three institutions participating in this application have a history of collaborative study of the availability and suitability of conceptal tissue for transplantation research. Together, they formed the Northwest Fetal Tissue Program that served as a grantee in the first NIH fetal tissue banking project. For over 30 years, the Central Laboratory for Human Embryology has been the only national resource fended by the NIH for collection, analysis and distribution of human conceptal tissue. It has collected and processed over 15,000 embryos and fetuses. The Northwest Tissue Center is a leader is tissue banking. It is accredited by the AATB and specializes in cryopreservation of a wide variety of transplant and research human allografts including autologous and cadaveric hematopoietic stem cells. It is the only tissue bank in the nation that procures, processes, cryopreserves and distributes such a wide range of allogeneic tissues. Bone marrow replacement therapy was developed at the Fred Hutchinson Cancer Research Center in Seattle, where research on and therapeutic use of stem cell replacement is ongoing. Together these institutions provide the breadth of background necessary for continued studies related to characterization of transplantable cells derived from embryonic liver.
