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Mast cell growth factor (c-kit ligand) supports the growth of human
multipotential progenitor cells with a high replating potential
CE Carow, G Hangoc, SH Cooper, DE Williams and HE Broxmeyer
Department of Microbiology and Immunology, Indiana University School of
Medicine, Indianapolis 46202-5121.
The replating capability of human multipotential (colony-forming unit-
granulocyte-erythrocyte-macrophage-megakaryocyte [CFU-GEMM]) and erythroid
(burst-forming unit-erythroid [BFU-E]) progenitors was assessed in vitro as
a potential measure of self-renewal using purified, recombinant (r) human
(hu) or murine (mu) mast cell growth factor (MGF), a ligand for the c-kit
proto-oncogene receptor. Primary cultures of human umbilical cord blood or
adult human bone marrow cells were initiated in methylcellulose with
erythropoietin (Epo) alone or in combination with rhu interleukin-3 (IL-3)
or MGF. Individual day 14 to 18 CFU-GEMM or BFU-E colonies were removed
from primary cultures and reseeded into secondary methylcellulose cultures
containing a combination of Epo, MGF, and rhu granulocyte-macrophage
colony- stimulating factor (GM-CSF). The data showed a high replating
efficiency of cord blood and bone marrow CFU-GEMM in response to Epo + MGF
in terms of the percentage of colonies that could be replated and the
number of secondary colonies formed per replated primary colony. The
average number of hematopoietic colonies and clusters apparent from
replated cultures of cord blood or bone marrow CFU-GEMM stimulated by Epo +
MGF was greater than with Epo + rhuIL-3 or Epo alone. Replated cord blood
CFU-GEMM gave rise to CFU-GEMM, BFU-E, and GM colony-forming units (CFU-GM)
in secondary cultures. Replated bone marrow CFU-GEMM gave rise mainly to
CFU-GM in secondary cultures. A more limited capacity for replating of cord
blood and bone marrow BFU-E was observed. These studies show that CFU-GEMM
responding to MGF have an enhanced replating potential, which may be
promoted by MGF. These studies also support the concept that MGF acts on
more primitive progenitors than IL-3.
Volume 78,
Issue 9,
pp. 2216-2221,
11/01/1991
Copyright © 1991 by The American Society of Hematology
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