"Serious disorders of the blood system, particularly malignant blood disorders and genetic diseases can be effectively treated by blood and marrow transplantation. Despite considerable success with this treatment modality during the last decades, lack of suitable donors, engraftment failure and graft versus host disease remain serious problems that need to be addressed. This project aims to address these issues through approaches that will allow expansion of human umbilical cord blood stem cells for transplantation using cytokines, developmental cues, newly identified stem cell regulators and chemicals that can activate internal stem cell regulators to stimulate self-renewal and proliferation of hematopoietic stem cells. Successful expansion of cord blood stem cells will increase the number of hematopoietic stem cells in cord blood samples to generate suitable donor samples for adult patients that die from their disease today due to lack of donors. Expansion of hematopoietic stem- and progenitor cells will also give more efficient early engraftment following transplantation and thereby reduce the frequency of morbidity and mortality due to insufficient engraftment. This will be accomplished through the identification of novel stem cell regulators and the use of known cytokines, developmental cues and chemicals that will stimulate stem cell expansion. Improvement in hematopoietic stem cell transplantation through co-transplantation of mesenchymal stem cells will also be investigated. Conditions for expansion of mesenchymal stem cells will be defined and subsets of more primitive and more mature mesenchymal stem cells will be identified. Mesenchymal stem cells will also be used to improve engraftment efficiency of the expanded hematopoietic cells and to reduce the frequency of graft versus host disease. The findings are expected to have a great impact on the treatment of serious blood disorders by blood and marrow transplantation in the future."