Effects of bestatin on myelopoietic stem cells in normal and cyclophosphamide-treated mice

The effect of bestatin on hematopoietic parameters and bone marrow progenitor activity (colony-forming unit - granulocyte/macrophage: CFU-GM) was examined in normal and myelosuppressed C57BL/6 mice. CFU-GM frequency and absolute number were determined with a limiting dilution analysis of bone marrow cells in soft agar using recombinant murine colony-stimulating factor - granulocyte/macrophage. We report that bestatin increased splenic, bone marrow, and peripheral blood cellularity and the number of CFU-GM over a dose range from 2.5 mg/kg through 100 mg/kg following i.p., i.v., or oral administration. The greatest myeloid stimulation was observed following multiple injections of bestatin. Bestatin also increased the recovery from cyclophosphamide-induced myelodepression as measured by these parameters. The hematopoietic properties of bestatin following oral administration is of potential importance for clinical application.