EXPANSION OF CORD-BLOOD PROGENITORS AND USE FOR HEMATOPOIETIC RECONSTITUTION

A high number of stem cells migrate in fetal blood and, at birth, the number of progenitors in cord blood equals or exceeds that of adult bo ne marrow. Recently hemopoiesis has been successfully reconstituted wi th the infusion of cord blood cells. It is important to clearly define the quantity and quality of cord blood totipotent and multilineage pr ogenitors to evaluate the possibility of their utilization in transpla nts. Our first aim was to study the growth characteristics of cord blo od progenitors. We have evaluated the number of cycling cells with the thymidine suicide technique and the production, by phytohemagglutinin (PHA) stimulated cord blood mononuclear cells, of some cytokines invo lved in the proliferation of progenitor cells, such as granulocyte-mac rophage colony stimulating factor (GM-CSF), interleukin 6 (IL-6) and l eukemia inhibitory factor (LIF). We have also studied by flow cytometr y the CD34+CD33-, CD34+CD33, cell subsets and the presence of the c-ki t receptor in order to quantitate the number of earlier progenitors. O ur second aim was to elucidate whether the cord blood totipotent stem cell population or the committed progenitors could be expanded in vitr o. Our results showed that in cord blood the number of early progenito rs, as evaluated by the number of mixed lineage colony forming units ( CFU-Mix), by the CD34+CD33- subsets and the expression of the c-kit, i s higher than in bone marrow. We have also demonstrated the possibilit y in vitro of increasing the number of progenitors by more than 30-fol d by utilizing stem cell factor (SCF) in association with other cytoki nes. These findings may be relevant for transplant practice since they offer the means to enhance hematopoietic recovery.