Objective: To determine if recombinant human hemangiopoietin (HAPO), a novel growth factor for primitive cells of hematopoietic and endothelial cell lineages, accelerates hematopoietic reconstitution after high-dose chemotherapy in vivo in mice.
Methods: Male Balb/c mice after treatment of 5-fluorouracil were subcutaneously injected with HAPO or its dilution for consecutive 10 d. Their survival and body weight together with peripheral blood were routinely tested. At day 7 and 14, the numbers of bone marrow (BM) cells as well as colony-forming units (CFU) after in vitro colony culture were counted. The peripheral blood CFU and the percentage of CD34+ CD117+ cells in BM were analyzed. Transwell chamber was used for cell migratory assay.
Results: HAPO at different doses significantly increased the survival rate and body weight, with an optimal effect in the HAPO 10 microg/d group. The number of BM cells and the percentage of CD34+ CD117+ cells were also increased after HAPO administration. The number of granulocyte/macrophage CFU and granulocyte, erythroid, macrophage and megakaryocyte CFU in BM after HAPO treatment was greater than that from the HAPO dilution group. More circulating CFU could be observed after injection of HAPO. In addition, this novel cytokine had a chemotactic effect on the hematopoietic stem/progenitor cells.
Conclusion: HAPO improves animal survival and accelerates hematopoietic reconstitution of mice after high-dose chemotherapy.