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Blood, 15 August 2001, Vol. 98, No. 4, pp. 1246-1251
TRANSPLANTATION
Host marrow stem cell potential and engraftability at varying
times after low-dose whole-body irradiation
F. Marc Stewart,
Suju Zhong,
Jean-François Lambert,
Gerald A. Colvin,
Mehrdad Abedi,
Mark S. Dooner,
Christina I. McAuliffe,
Han Wang,
Chung Hsieh, and
Peter J. Quesenberry
From the University of Massachusetts Cancer Center,
Worcester; and Department of Research, Roger Williams Medical Center,
Providence, RI.
High levels of chimerism in syngeneic BALB/c transplants
were reported when hosts were exposed to 1 Gy (100 cGy) whole body irradiation (WBI) and infused with 40 × 106 marrow
cells. The recovery of host stem cells and alterations of enhanced host
engraftability at varying times after 1 Gy WBI have now been evaluated
in this study. Male BALB/c marrow (40 × 106 cells) was
infused into female BALB/c hosts immediately or at 6, 12, and 24 weeks
after 1 Gy WBI of host female BALB/c mice; engraftment percentages 8 weeks after cell injection at week 0, 6, 12, or 24 were 68% ± 12%,
45% ± 15%, 51% ± 12%, or 20% ± 8%, respectively.
Eight-week engraftment levels in nonirradiated hosts average 7.7%.
Conversely, engraftable stem cells measured at 8 weeks
postengraftment in 1 Gy- exposed hosts were reduced to
8.6% ± 3% of nonirradiated mice at time 0, 35% ± 12% 6 weeks later, 49% ± 10% at 3 months, and 21% ± 7% at 6 months. Engraftment was still increased and stem cell decreased 1 year
after 1 Gy. Furthermore, the primary cells transplanted into 1 Gy hosts
can be serially transplanted, and the predominant effect of 1 Gy is
directly on engrafting stem cells and not through accessory cells.
These data show that transplantation in 1 Gy mice may be delayed until
recovery of hematopoiesis, suggesting strategies in allogeneic
transplantation to avoid the adverse effects of cytokine storm. The
incomplete recovery of engraftable stem cells out to 12 months
indicates that stem cell expansion, especially in patients previously
treated with radiomimetic drugs, may not be feasible.
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