Tresperimus, an analogue of 15-deoxyspergualine (15-DSG), has been found, in rodents, to induce a potent state of tolerance after organ and bone marrow allografts. In a previous study, we have reported that
tresperimus at the optimal concentration of 0.5 microgram/ml supports the clonogenic potential of human cord blood CD34+ cells. Dose dependent inhibition of clonogenesis was also observed with complete reversibility following
drug withdrawal. In this study, we tested the effect of 0.5 microgram
tresperimus/ml on ex vivo expansion of primitive human cord blood CD34+CD38- cells. Our findings revealed that the total number of expanded cells was decreased in the presence of
tresperimus. However, the multipotential and erythroid colonies were significantly increased in the presence of
tresperimus compared with control cultures done without the test
drug. Progenitor cell morphology was comparable in both test and control cultures. The
telomerase activity was consistently lower in
tresperimus-treated hematopoietic progenitors than in control cultures. These results suggest that
tresperimus preserves primitive CD34+CD38- cells in a state of high potentiality while limiting the total number of their differentiated progeny. Bearing in mind that the test
drug supports the clonogenic potential of CD34+ cells, the overall findings emphasize the importance of assessing the effect of
tresperimus on in vivo long-term hematopoiesis which could predict the potential clinical use of
tresperimus in the prevention of
graft-versus-host disease in recipients of allogeneic bone marrow.