The results of autologous and allogeneic peripheral blood stem cell (PBSC) transplants suggest that recruited hematopoietic stem cells (HSC) may have qualities that could make them more competitive than adult marrow HSC, particularly when applied to in utero transplantation. In preparation for assessing the use of recruited PBSC in our rhesus in utero transplantation model, we studied the response of rhesus monkeys to administration of recombinant human stem cell factor (SCF) and granulocyte-colony stimulating factor (G-CSF). Four monkeys were injected once daily for 14 days with SCF, G-CSF, or a combination of G-CSF+SCF. Blood and bone marrow samples were obtained at varying time points before, during, and after administration, and white blood cell counts (WBCs), differentials, CD34+ stem cells, and progenitors were assessed. Clinical chemistries were also performed to monitor renal and hepatic function. Results showed dramatic increases in WBCs and absolute neutrophil counts in recipients of either G-SCF or G-CSF+SCF within 3 days of treatment initiation, with a synergistic rise in the leukocyte populations with G-CSF+SCF. There were no effects of SCF or G-CSF on platelets, lymphocytes, erythrocyte counts, or T-cell subpopulations. Upon evaluation of the HSC population, a significant increase in the total number of CD34+ cells was found by day 6 of treatment in the animals receiving G-CSF or G-CSF+SCF, which declined to baseline levels upon termination of treatment. SCF alone resulted in a rise in CD34+ cells on day 10 of treatment which returned to baseline by day 14. While there was no obvious difference between G-CSF and G-CSF+SCF with respect to CD34+ cells in the blood, there was a greater number of myeloid progenitor cells (CFU-GM) in the G-CSF+SCF animals compared to those receiving G-CSF alone. These preliminary results indicate that rhesus monkeys respond to these recombinant human hematopoietic growth factors and that there are no obvious toxicities associated with treatment. *KEY*Hematopoietic stem cells, CD34, SCF, G-CSF, Transplantation

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR000169-35
Application #
5219972
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
35
Fiscal Year
1996
Total Cost
Indirect Cost
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