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Prepublished online as a Blood First Edition Paper on May 29, 2003; DOI 10.1182/blood-2002-12-3742.
Submitted December 10, 2002
Accepted May 8, 2003
Distribution of marrow repopulating cells between bone marrow and spleen early after transplantation
P Artur Plett, Stacy M Frankovitz, and Christie M Orschell*
Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
* Corresponding author; email: corschel{at}iupui.edu.
Whether hematopoietic stem cells (HSC) home selectively to bone marrow (BM) early after transplantation remains an issue of debate. Better understanding of homing mechanisms may benefit BM transplantation protocols in cases of limited graft cell number or non-myeloablative conditioning regimens. Using flow cytometry and serial transplantation to stringently identify HSC, trafficking patterns of long-term engrafting cells were mapped between BM and spleen early after transplantation. Low density BM cells were tracked in irradiated or non-irradiated mice 1, 3, 6 and 20hr after transplantation, at which time recipient BM and spleen were analyzed for recovery of primitive donor cells by phenotype and adhesion molecule expression. In addition, phenotypically-defined HSC-enriched or HSC-depleted grafts were tracked 20hr after transplantation in recipient BM and spleen, and analyzed for recovery and long-term repopulating potential in serially-transplanted mice. Regardless of irradiation status, recovery of donor Sca-1+lin- cells was higher at most time points in recipient BM than in spleen, while recovery of total Sca-1+ cells was variable. A significantly higher percentage of BM-homed donor Sca-1+ cells expressed CD43, CD49e and CD49d 20hr after transplantation than spleen-homed cells, which contained significantly more non-HSC phenotypes. Furthermore, BM-homed cells were significantly enriched for cells capable of secondary multi-lineage hematopoiesis in serially-transplanted mice compared to spleen-homed cells. These results support the notion of specific homing of HSC to BM by 20hr after transplantation, and provide a basis for the enhanced engraftment potential afforded some Sca-1+lin- cells subfractionated on the basis of adhesion molecule expression.
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