Accelerated hematopoietic recovery with the hemoregulatory peptide dimer SK&F 107647 in bone marrow transplantation

The effect of a novel hemoregulatory peptide SK&F107647 on recovery of hematopoiesis was studied in murine bone marrow transplantation (BMT) models. In the first model, lethally irradiated recipient mice were transplanted with 10(6) bone marrow cells from donors given a single injection of either SK&F107647 or PBS 2 days prior to transplantation. The femoral content of GM-CFC was shown to be almost twice as high in mice treated with SK&F107647 compared with controls. Both the marrow GM-CFC progenitor cell population and Mac-1 positive cells in blood were shown to recover faster in recipients of SK&F107647 treated donors. The use of SK&F107647 treated donors did not result in significantly faster blood cell count recovery in the recipient mice. In the second model, lethally irradiated recipients were transplanted with normal bone marrow cells (10(5)-10(6) and then given daily injections of SK&F107647 for 10 days starting 1 day after transplantation. The results show significantly enhanced recovery of GM-CFC in spleen and bone marrow and enhanced numbers of mature Mac-1 positive cells in spleen and peripheral blood. In addition, Thy1.2 positive cells recovered faster in SK&F107647 treated animals compared with controls. The results from these models suggest a role for SK&F107647 in BMT either as a primer of the marrow before transplantation or as an enhancer of hematopoietic recovery when given therapeutically after transplantation.