|
|
Blood, 1 May 2006, Vol. 107, No. 9, pp. 3764-3771.
Prepublished online as a Blood First Edition Paper on January 26, 2006; DOI 10.1182/blood-2005-09-3593.
 Previous Article | Table of Contents | Next Article 
TRANSPLANTATION
Mobilization as a preparative regimen for hematopoietic stem cell transplantation
Jing Chen,
André Larochelle,
Simon Fricker,
Gary Bridger,
Cynthia E. Dunbar, and
Janis L. Abkowitz
From the Medicine/Hematology, University of Washington, Seattle, WA; Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD; and AnorMED, Langley, BC, Canada.
Current myeloablative conditioning regimens for hematopoietic stem cell (HSC) transplantation are associated with significant morbidity and mortality. Thus, alternative strategies to promote engraftment of infused HSCs with increased safety warrant investigation. Using parabiotic mice, we determined that, after mobilization with AMD3100 (a CXCR4 antagonist), HSCs exited from marrow, transited blood, and engrafted in open niches in partner marrow. We then hypothesized that mobilization before transplantation might vacate niches and improve HSC engraftment. When PeP3b mice were treated with AMD3100 at 2 hours before the transplantation of 4 x 107 marrow cells, donor cell engraftment was higher (4.6% ± 1.1%) than in control animals (no AMD3100; 1.0% ± 0.24%, P < .001). When mice received weekly injections of AMD3100 on 3 consecutive weeks and marrow cells were transplanted 2 hours after each mobilization, donor cell engraftment further increased (9.1% ± 1.7%, P = .001). In contrast, in similar experiments with Balb/cByJ mice that mobilize poorly, there was no difference between the donor cell engraftment of AMD3100-treated and control recipients. These results indicate that the number of available niches regulates the number of HSCs. In addition, mobilization with AMD3100 may provide a safer preparative approach for HSC transplantation in genetic and other nonmalignant disorders.
View this table:
[in this window]
[in a new window]
|
Table 1.. Trafficking of granulocytes, CFU-GMs, and HSCs in marrow of parabiotic mice at baseline and after cytokine or AMD3100 mobilization
|
|
View this table:
[in this window]
[in a new window]
|
Table 3.. Trafficking of granulocytes, CFU-GMs, and HSCs in spleen, marrow, and blood of parabiotic mice at baseline and after cytokine or AMD3100 mobilization
|
|
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
Related Article in Blood Online:
-
AMD3100 mobilizes hematopoietic stem cells with long-term repopulating capacity in nonhuman primates
- André Larochelle, Allen Krouse, Mark Metzger, Donald Orlic, Robert E. Donahue, Simon Fricker, Gary Bridger, Cynthia E. Dunbar, and Peiman Hematti
Blood 2006 107: 3772-3778.
[Abstract]
[Full Text]
[PDF]
This article has been cited by other articles:
|
|
|
|
 
Z. Wang, G. Li, W. Tse, and K. D. Bunting
Conditional deletion of STAT5 in adult mouse hematopoietic stem cells causes loss of quiescence and permits efficient nonablative stem cell replacement
Blood,
May 14, 2009;
113(20):
4856 - 4865.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. L. Abkowitz and J. Chen
Studies of c-Mpl function distinguish the replication of hematopoietic stem cells from the expansion of differentiating clones
Blood,
June 15, 2007;
109(12):
5186 - 5190.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Barese, N. Pech, S. Dirscherl, J. L. Meyers, A. L. Sinn, M. C. Yoder, W. S. Goebel, and M. C. Dinauer
Granulocyte Colony-Stimulating Factor Prior to Nonmyeloablative Irradiation Decreases Murine Host Hematopoietic Stem Cell Function and Increases Engraftment of Donor Marrow Cells
Stem Cells,
June 1, 2007;
25(6):
1578 - 1585.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
