TY - JOUR
T1 - Host marrow stem cell potential and engraftability at varying times after low-dose whole-body irradiation
AU - Marc Stewart, F.
AU - Zhong, Suju
AU - Lambert, Jean François
AU - Colvin, Gerald A.
AU - Abedi, Mehrdad
AU - Dooner, Mark S.
AU - McAuliffe, Christina I.
AU - Wang, Man
AU - Hsieh, Chung
AU - Quesenberry, Peter J.
PY - 2001/8/15
Y1 - 2001/8/15
N2 - 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 × 10 6 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 × 10 6 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 Gyexposed 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.
AB - 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 × 10 6 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 × 10 6 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 Gyexposed 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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U2 - 10.1182/blood.V98.4.1246
DO - 10.1182/blood.V98.4.1246
M3 - Article
C2 - 11493477
AN - SCOPUS:0035883105
VL - 98
SP - 1246
EP - 1251
JO - Blood
JF - Blood
SN - 0006-4971
IS - 4
ER -