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The ligand for c-kit, stem cell factor, stimulates the circulation of cells
that engraft lethally irradiated baboons
RG Andrews, WI Bensinger, GH Knitter, SH Bartelmez, K Longin, ID Bernstein, FR Appelbaum and KM Zsebo
Program in Pediatric Oncology, Fred Hutchinson Cancer Research Center,
Seattle, WA 98104.
Recombinant human stem cell factor (SCF), the ligand for c-kit, has been
shown to stimulate increased numbers of hematopoietic progenitor cells of
multiple types to circulate in the blood of baboons, but it was not known
if the cells stimulated to circulate by SCF contained cells capable of
engrafting and rescuing lethally irradiated baboons. Peripheral blood
mononuclear cells (PBMNC) were collected by leukapheresis from four
untreated control baboons and from three baboons on the 10th or 11th day of
treatment with SCF (200 micrograms/kg/d). All animals were transplanted
with 1.00 to 1.04 x 10(8)/kg of cryopreserved autologous PBMNC after
treatment with a single dose of 1,020 cGy total body irradiation (TBI).
Three animals were transplanted with PBMNC that had been collected during
SCF treatment, 24 to 38 days after the last dose of SCF. Rapid trilineage
engraftment was documented by bone marrow biopsy in all three. The mean
time to a total white blood cell count (WBC) > or = 500/microL, WBC >
or = 1,000/microL, and an absolute neutrophil count (ANC) > or =
500/microL was 15 +/- 3 (mean +/- SD), 19 +/- 1, and 19 +/- 2 days,
respectively. Two animals remain alive with stable engraftment more than
180 and 245 days posttransplant. The third died of sepsis 32 days
posttransplant with a hypercellular marrow showing trilineage engraftment.
The surviving animals were transfusion independent by 10 and 59 days
posttransplant. Four control animals were transplanted with PBMNC collected
in the absence of SCF stimulation. One was treated for 11 days with SCF
(200 micrograms/kg/d) after PBMNC were collected. This animal was
transplanted 25 days after the last dose of SCF. None of the four control
animals engrafted and they died 13, 16, 28, and 38 days posttransplant with
marrow aplasia. Treatment with SCF stimulates the circulation of cells that
engraft and rescue lethally irradiated baboons. The characteristics of the
transplantable cells present in the circulation are now amenable to direct
study.
Volume 80,
Issue 11,
pp. 2715-2720,
12/01/1992
Copyright © 1992 by The American Society of Hematology
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