Enhancement of human hematopoiesis by mast cell growth factor in human-sheep chimeras created by the in utero transplantation of human fetal hematopoietic cells.
We have previously described a unique model of long-term, multilineage, human hematopoietic chimerism in sheep created by the in utero transplantation of human hematopoietic stem cells (HSC) into pre-immune fetal lambs. In this study, we examined the effect of chronic administration of recombinant human mast cell growth factor (rhMGF) on 1) human cell engraftment in pre-immune sheep and 2) human cell expression in human-sheep chimeras at 2-years posttransplant. rhMGF (25 micrograms/kg) or saline was administered in utero via chronic intraperitoneal (IP) catheters to three separate sets of twin fetuses on alternate days for 10 doses following transplantation of human HSC. Flow-cytometric and karyotype analyses of peripheral blood from two sets of twins at 45-days posttransplant 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 micrograms/kg/day) was also administered by IP injection to two, 2 year-old, human-sheep chimeras for 18 consecutive days. Flow-cytometric analysis of peripheral blood and bone marrow revealed a six- to seven-fold increase in human cell expression. The effect on early human progenitors (i.e., colony-forming unit-mix [CFU-Mix], CFU granulocyte/macrophage [CFU-GM], and burst-forming unit-erythroid [BFU-E]) was determined by karyotype analysis of individual colonies grown under conditions favoring human cell growth. A three- to five-fold increase in human CFU-Mix and BFU-E occurred with a minimal increase in CFU-GM. This in vivo study supports in vitro data suggesting that MGF is a powerful regulator of human hematopoiesis and preferentially stimulates early hematopoietic progenitors. It also supports the potential value of the human-sheep model for the in vivo study of normal and abnormal human hematopoiesis.
Flake
A W
AW
Department of Surgery, University of California, San Francisco.
Hendrick
M H
MH
Rice
H E
HE
Tavassoli
M
M
Zanjani
E D
ED
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D017690:Cell Transplantation; D005314:Embryonic and Fetal Development; D005260:Female; D006410:Hematopoiesis; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D011247:Pregnancy; D012756:Sheep / Q000196:embryology; D019089:Stem Cell Factor; D014599:Uterus / Q000166:cytology
D016298:Hematopoietic Cell Growth Factors; D019089:Stem Cell Factor