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Blood, 1 October 2001, Vol. 98, No. 7, pp. 2108-2115
HEMATOPOIESIS
Differential homing and engraftment properties of hematopoietic
progenitor cells from murine bone marrow, mobilized peripheral blood,
and fetal liver
Stephen J. Szilvassy,
Todd
E. Meyerrose,
Penny L. Ragland, and
Barry Grimes
From the Blood and Marrow Transplant Program, and the
Division of Hematology/Oncology, Lucille P. Markey Cancer Center,
University of Kentucky, Lexington, Kentucky.
The rate of reconstitution following hematopoietic stem cell (HSC)
transplantation differs widely depending on the tissue source of the
cells infused. To test the hypothesis that variability in engraftment
kinetics is related to differences in the efficiency with which
intravenously transplanted HSCs "home" to the bone marrow (BM), the
homing properties of murine fetal liver (FL), adult BM, and mobilized
peripheral blood (MPB) cells were compared. Lethally irradiated mice
transplanted with 2 × 106 FL, BM, or MPB cells exhibited
sequentially slower recovery of circulating leukocytes and platelets
that correlates with the progressively lower frequency of
colony-forming cells (CFCs) in these tissues. However, differences in
the rate and degree of early and long-term reconstitution were
maintained even after infusing equal numbers of CFCs derived from FL,
BM, and MPB. To compare the homing of progenitors from these tissues,
cells were labeled with fluorescent PKH26 dye and injected into
lethally irradiated hosts. Three hours later, PKH26+ cells
were reisolated from the BM and spleen by fluorescence-activated cell
sorting and assayed for in vitro CFCs. Despite the higher level of very
late antigen (VLA)-2, VLA-4, and VLA-5 on
Sca-1+c-kit+ cells from FL compared to BM,
10-fold fewer FL CFCs homed to hematopoietic organs than those from BM.
MPB cells homed slightly better, but still less efficiently than BM
cells. Therefore, clonogenic cells from different tissues exhibit
striking variations in homing efficiency that does not necessarily
correlate with engraftment kinetics. Homing is likely counterbalanced
by intrinsic differences in proliferative potential that ultimately
determine the rate of hematopoietic reconstitution.
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