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Blood, 15 November 2002, Vol. 100, No. 10, pp. 3545-3552
HEMATOPOIESIS
In vivo trafficking, cell cycle activity, and engraftment
potential of phenotypically defined primitive hematopoietic cells after
transplantation into irradiated or nonirradiated
recipients
P. Artur Plett,
Stacy M. Frankovitz, and
Christie M. Orschell-Traycoff
From the Department of Medicine, Indiana University
School of Medicine, Indianapolis, IN.
Recent interest in bone marrow (BM) transplantation in
nonconditioned or minimally conditioned recipients warrants
investigation of homing patterns of transplanted hematopoietic
progenitor cells (HPCs) in irradiated and nonirradiated recipients. To
this end, phenotypically defined populations of BM cells were tracked
in lethally irradiated or nonirradiated mice at 1, 3, 6, and 24 hours after transplantation. Recovery of transplanted cells at all time points was higher in BM of nonirradiated mice, similar to earlier suggestions. The percentage of lineage-negative Sca-1+
cells and Sca-1+ cells expressing CD43, CD49e, and CD49d
steadily increased in BM of nonirradiated mice up to 24 hours, while
fluctuating in irradiated mice. Cell cycle status and BrdU
incorporation revealed that less than 20% of Sca-1+ cells
and fewer Sca-1+lin cells had cycled by 24 hours after transplantation. To more directly examine trafficking of
primitive HPCs, purified grafts of CD62L or
CD49e+ subfractions of Sca-1+lin
cells, previously shown to be enriched for long-term repopulating cells, also were tracked in vivo. Recovery of purified cells was similarly increased in BM of nonirradiated mice. When 50 to 100 of
these BM-homed cells were examined in serial transplantation studies,
BM-homed cells from initially nonirradiated mice were enriched 5- to
30-fold for cells capable of long-term hematopoiesis in secondary
recipients. Collectively, these data suggest that homing or survival of
transplanted cells in irradiated recipients is less efficient than that
in nonirradiated recipients, implicating an active role of
radiation-sensitive microenvironmental cues in the homing process.
These results may have important clinical implications in the design of
BM transplantation protocols.
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