Modulation of ex-vivo expanded human cord blood graft and mobilization of peripheral blood progenitor cells

다국어 초록 (Multilingual Abstract)

Human umbilical cord blood(CB) is an alternative source of hematopoietic stem cell(HSC). However, the use of CB is limited by a delayed engraftment due to insufficient number of HSCs. Cytokine-mediated ex vivo expansion has been proposed as a means of increasing the number of CB HSCs for transplantation. However, the biology of CB HSCs during cytokine-mediated ex vivo expansion, such as apoptosis or expression of adhesion molecules, has not yet been elucidated.
Human cord blood ex-vivo exansion system has been established using TPO, FL and G-CSF with/without feeder layer. In addition, by understanding the molecular mechanisms of apoptosis during ex-vivo expansion, we are able to build up more efficient ex-vivo system. In result, we can provide not only more hematopoietic stem cells(quantity) but "true stem cells" having better qualities.
Bone marrow hematopoietic stem cell transplantation has been very powerful curative method for disease, i.e., leukemia, aplastic anemia and metabolic disease. Meanwhile, peripheral blood hematopoietic stem cells have been alternative sources for allogeneic transplantation. However, it takes 5-6 days to get optimal mobilization using cytokines like G-CSF. Though many transplantation centers have been using mobilized peripheral blood hematopoietic stem cell for allograft on curing hematopoietic malignancies, the optimal protocols for mobilization and its mechanisms on mobilization need to be elucidated. We would like to focus two areas. First, we would like to set up the speedy methods for mobilization using different cytokines, anti CAMs and proteinase inhibitors. Same time, we would like to figure out the way how to collect the large number("Mega" dose) of CD34+ cells. Second, the molecular mechanism of mobilization and its signal transduction pathways will be investigated.
In results, we may apply our knowledges that we will obtain via this current projects to the clinic for the situations that we need to overcome the MHC barries(HLA-mismatch setting) with megadose CD34+ cells. And understanding the molecular mechanisms on mobilization may provide the insight for finding more specific molecules with having less sides effects on mobilization in near future.