ENHANCEMENT OF HUMAN HEMATOPOIESIS BY MAST-CELL GROWTH-FACTOR IN HUMAN-SHEEP CHIMERAS CREATED BY THE IN-UTERO TRANSPLANTATION OF HUMAN FETAL HEMATOPOIETIC-CELLS
Aw. Flake et al., ENHANCEMENT OF HUMAN HEMATOPOIESIS BY MAST-CELL GROWTH-FACTOR IN HUMAN-SHEEP CHIMERAS CREATED BY THE IN-UTERO TRANSPLANTATION OF HUMAN FETAL HEMATOPOIETIC-CELLS, Experimental hematology, 23(3), 1995, pp. 252-257
We have previously described a unique model of long-term, multilineage
, human hematopoietic chimerism in sheep created by the in utero trans
plantation of human hematopoietic stem cells (HSC) into pre-immune fet
al lambs. In this study, we examined the effect of chronic administrat
ion of recombinant human mast cell growth factor (rhMGF) on 1) human c
ell engraftment in pre-immune sheep and 2) human cell expression in hu
man-sheep chimeras at 2-years posttransplant. rhMGF (25 mu g/kg) or sa
line was administered in utero via chronic intraperitoneal (IP) cathet
ers to three separate sets of twin fetuses on alternate days for 10 do
ses following transplantation of human HSC. Flow-cytometric and karyot
ype analyses of peripheral blood from two sets of twins at 45-days pos
ttransplant and of peripheral blood from the remaining set of twins at
birth revealed a significant increase in percentages of donor (human)
progenitors and cells in rhMGF-treated lambs. rhMGF (60 mu g/kg/day)
was also administered by IP injection to two, 2 year-old, human-sheep
chimeras for 18 consecutive days. Flow-cytometric analysis of peripher
al blood and bone marrow revealed a six- to seven-fold increase in hum
an cell expression. The effect on early human progenitors (i.e., colon
y-forming unit-mix [CFU-Mix], CFU granulocyte/macrophage [CFU-GM], and
burst-forming unit-erythroid [BFU-E]) was determined by karyotype ana
lysis of individual colonies grown under conditions favoring human cel
l growth. A three- to five-fold increase in human CFU-Mix and BFU-E oc
curred with a minimal increase in CFU-GM. This in vivo study supports
in vitro data suggesting that MGF is a powerful regulator of human hem
atopoiesis and preferentially stimulates early hematopoietic progenito
rs. It also supports the potential value of the human-sheep model for
the in vivo study of normal and abnormal human hematopoiesis.