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Prepublished online as a Blood First Edition Paper on July 12, 2002; DOI 10.1182/blood-2002-04-1256.
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Blood, 15 November 2002, Vol. 100, No. 10, pp. 3521-3526
HEMATOPOIESIS
Murine hematopoietic stem cell distribution and proliferation in
ablated and nonablated bone marrow transplantation
Jiang F. Zhong,
Yuxia Zhan,
W. French Anderson, and
Yi Zhao
From the Gene Therapy Laboratories, the Department of
Biochemistry and Molecular Biology, and the Division of Hematology of
the Department of Medicine, Keck School of Medicine, University of
Southern California, Los Angeles.
The engraftment of donor bone marrow (BM) cells in nonablated mice
is inefficient. Niche availability has been thought to be the reason,
and cytoablation with irradiation or cytotoxic agents is routinely used
with the belief that this frees the preoccupied niches in recipients.
In this study, donor cell redistribution and proliferation in ablated
and nonablated mice were compared by implanting donor cells directly
into the femur cavity of sedated mice. The redistribution of
Lin donor cells into BM was similar between ablated and
nonablated mice. Poor engraftment in nonablated mice was shown to be
the result of inefficient donor cell proliferation rather than because of a lack of space. Competitive repopulation assays demonstrated that
the donor hematopoietic stem cells (HSCs) were present in nonirradiated
recipients for at least 6 months after transplantation, but that they
did not expand as did their counterparts in lethally irradiated mice.
This study suggests that efficient bone marrow transplantation in
nonablated recipients may be possible as a result of better
understanding of HSC proliferative regulation and appropriate in vitro manipulation.
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