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Liver-derived fetal hematopoietic stem cells selectively and preferentially
home to the fetal bone marrow
ED Zanjani, JL Ascensao and M Tavassoli
Department of Veterans Affairs Medical Center, Reno, NV 89520.
In the course of ontogeny, the homing site for the hematopoietic stem cells
(HSC) moves with certain predictability from the yolk sac to the
liver/spleen and then to the marrow. The pattern of this migration has thus
far been established mostly on a morphologic basis. To delineate further
the course of this migration and to gain insight into its possible
mechanism, we used in utero transplantation of allogeneic or xenogeneic HSC
in preimmune sheep fetuses. Sex chromosome, type of hemoglobin, and
species-specific surface markers were used to follow the path of
transplanted cells in the fetus. Before the development of the bone marrow,
transplanted HSC (liver- or marrow-derived) homed exclusively to the
liver/spleen. With the development of marrow, around day 60 of gestation
(term, 145 days), homing occurred also in the nascent marrow and by day 80
transplanted cells homed exclusively to the marrow. This suggests that
there may be a hierarchy in homing sites, with those of the marrow having
higher affinity than those of liver/spleen. Interestingly, despite a change
in homing that was followed by the expansion of the marrow compartment of
HSC (ie, HSC proliferation), these cells did not participate actively in
blood cell formation during most of the prenatal period. Liver remained the
major hematopoietic organ throughout the gestation. It was only during the
perinatal period that this organ assumed the function of hematopoiesis from
the liver. This lack of expression of HSC in fetal marrow can possibly be
attributable to the immaturity of marrow stroma required for
differentiation and maturation of progenitors and the orderly egress of
mature cells into the blood stream. The availability of this model allows
us to begin studies in the molecular mechanism of stem cell homing in vivo
during ontogeny.
Volume 81,
Issue 2,
pp. 399-404,
01/15/1993
Copyright © 1993 by The American Society of Hematology
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