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Blood, Vol. 94 No. 9 (November 1), 1999:
pp. 3251-3257
A Kinetic Model for the Homing and Migration of Prenatally
Transplanted Marrow
Aimen F. Shaaban,
Heung Bae Kim,
Ross Milner, and
Alan W. Flake
From The Center for Fetal Diagnosis and Treatment at the Children's
Hospital of Philadelphia, Philadelphia, PA.
Currently little is known about the mechanisms regulating the homing
and the early engraftment of prenatally transplanted hematopoietic
cells due to the lack of a relevant functional assay. In this study, we
have defined a reproducible kinetic profile of the homing and the early
engraftment events in a murine model of prenatal stem cell
transplantation. Light density mononuclear cells (LDMCs) from adult
C57Pep3b and SJL/J marrow were transplanted by intraperitoneal (IP)
injection into C57BL/6 fetuses (106 LDMCs/fetus) at 14 days
of gestation. The fetuses were sacrificed at early time points (1.5 to
96 hours) after transplantation. Recipient fetal liver and cord blood
were analyzed for donor cell frequency and donor cell phenotype by dual
color flow cytometry. Pertinent findings included the following: (1) a
triphasic kinetic profile exists after in utero hematopoietic stem cell
(HSC) transplantation (homing of circulating donor cells, rapid
reduction of donor cell frequency, and donor cell competitive
equilibration); (2) homing to the fetal liver is nonselective and
reflects the phenotypic profile of the donor population; and (3) the
kinetics after the prenatal transplantation of congenic or fully
allogeneic cells are identical. This model will facilitate a systematic
analysis of the mechanisms that regulate the homing of prenatally
transplanted hematopoietic cells.
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