ADENOVIRUS-MEDIATED TRANSFER OF THE HST-1 (FGF4) GENE INDUCES INCREASED LEVELS OF PLATELET COUNT IN-VIVO

The HST-1 (fibroblast growth factor 4, FGF4) protein is a potent mitog en for a variety of cell types of mesodermal and neuroectodermal origi n, including fibroblasts, endothelial cells, and melanocytes in vitro. To identify the cells and tissue targets of HST-1 in vivo, adenovirus -mediated HST-1 gene transfer was performed. In nude mice, intraperito neal injection of 3 x 10(9) plaque-forming units of adenoviruses carry ing the HST-1 gene (Adex1HST-1L) caused an increase in the number of p latelets in the peripheral blood. The number of platelets reached twic e the pretreated level by 12 days after the virus injection and the in creased level continued up to 20-30 days thereafter. Administration of recombinant HST-1 protein resulted in a transient increase in the pla telet count. The number of megakaryocytes in the bone marrow and splee n of the animals with Adex1HST-1L was increased compared with the cont rol animals. Other hematological changes attributed to HST-1 were not observed. Although the mechanisms involved in increased levels of plat elet count by HST-1 protein remain to be elucidated, these findings al so suggest that adenovirus with the HST-1 gene may be efficiently used for the treatment of thrombocytopenia in various diseases.