Effective prevention of thrombocytopenia using adenovirus-mediated transfer of HST-11FGF-4 gene: in vivo and in vitro studies.

A novel biological function of HST-1 protein (FGF-4) was investigated by constructing an adenovirus vector containing the HST-1 cDNA and applied for thrombocytopenia as a gene therapy. A single intraperitoneal injection of the replication-deficient adenovirus containing the HST-1 gene (Adex1HST-1) into mice caused a two-fold increase in peripheral platelet count for 30 days, and effectively prevented experimentally induced thrombocytopenia. Studies of Adex1HST-1-infected or HST-1 protein-treated megakaryocytic Dami cells suggested that HST-1 protein promotes megakaryocyte maturation, and increases cytokine secretion from megakaryocyte and adhesive interactions between megakaryocyte and endothelial cells. Colony assay revealed that HST-1 protein stimulated CFU-MK (colony-forming unit of megakaryocyte) not alone but synergistically with early-acting cytokines such as IL-3 or Tpo (c-mpl ligand) as a megakaryocyte potentiating factor. These results have important implications for clinical application of the Adex1HST-1 for thrombocytopenia.