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Blood, 1 March 2002, Vol. 99, No. 5, pp. 1585-1593
HEMATOPOIESIS
Homing efficiency, cell cycle kinetics, and survival of quiescent
and cycling human CD34+ cells transplanted into conditioned
NOD/SCID recipients
Anna Jetmore,
P. Artur Plett,
Xia Tong,
Frances M. Wolber,
Robert Breese,
Rafat Abonour,
Christie M. Orschell-Traycoff, and
Edward F. Srour
From the Departments of Medicine and Pediatrics, Herman
B Wells Center for Pediatric Research and the Department of
Microbiology/Immunology, Indiana University School of Medicine,
Indianapolis.
Differences in engraftment potential of hematopoietic stem cells
(HSCs) in distinct phases of cell cycle may result from the inability
of cycling cells to home to the bone marrow (BM) and may be influenced
by the rate of entry of BM-homed HSCs into cell cycle. Alternatively,
preferential apoptosis of cycling cells may contribute to their low
engraftment potential. This study examined homing, cell cycle
progression, and survival of human hematopoietic cells transplanted
into nonobese diabetic severe combined immunodeficient (NOD/SCID)
recipients. At 40 hours after transplantation (AT), only 1% of
CD34+ cells, or their G0
(G0CD34+) or G1
(G1CD34+) subfractions, was detected in the BM
of recipient mice, suggesting that homing of engrafting cells to the BM
was not specific. BM of NOD/SCID mice receiving grafts containing
approximately 50% CD34+ cells harbored similar numbers of
CD34+ and CD34 cells, indicating that
CD34+ cells did not preferentially traffic to the BM.
Although more than 64% of human hematopoietic cells cycled in culture
at 40 hours, more than 92% of cells recovered from NOD/SCID marrow
were quiescent. Interestingly, more apoptotic human cells were detected at 40 hours AT in the BM of mice that received xenografts of expanded cells in S/G2+M than in recipients of
G0/G1 cells (34.6% ± 5.9% and
17.1% ± 6.3%, respectively; P < .01). These results
suggest that active proliferation inhibition in the BM
of irradiated recipients maintains mitotic quiescence
of transplanted HSCs early AT and may trigger apoptosis of cycling
cells. These data also illustrate that trafficking of transplanted
cells to the BM is not selective, but lodgment of BM-homed cells may be specific.
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