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Prepublished online as a Blood First Edition Paper on July 12, 2002; DOI 10.1182/blood-2002-04-1256.
Submitted April 29, 2002
Accepted June 28, 2002
Murine Hematopoietic Stem Cell Distribution and Proliferation in Ablated and Nonablated Bone Marrow Transplantation
Jiang F Zhong, Yuxia Zhan, French W Anderson, and Yi Zhao*
Biochemistry and Molecular Biology, University of Southern California, Keck School of Medicine, Los Angeles, California, USA; Gene Therapy Laboratories, University of Southern California, Keck School of Medicine, Los Angeles, California, USA
Gene Therapy Laboratories, University of Southern California, Keck School of Medicine, Los Angeles, California, USA
Division of Hematology of the Department of Medicine, University of Southern California, Keck School of Medicine, Los Angeles, California, USA; Gene Therapy Laboratories, University of Southern California, Keck School of Medicine, Los Angeles, California, USA
* Corresponding author; email: yizhao{at}usc.edu.
The engraftment of donor bone marrow (BM) cells in non-ablated 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 pre-occupied niches in recipients. In this study, donor cell redistribution and proliferation in ablated and non-ablated 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 non-ablated mice. Poor engraftment in non-ablated 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 (HSC) were present in non-irradiated 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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