TBI with lung dose reduction does not improve hematopoietic cell homing to BM during allogeneic transplantation.
To determine the effects of TBI dose, fractionation and lung shielding on hematopoietic stem cell homing to the BM, BM cells were extracted from tibiae and femurs of B6-green fluorescent protein (GFP) mice and transplanted into B6 mice. Recipient mice had either: (i) no radiation, (ii) single-dose TBI at 13.6 Gy, (iii) single-dose TBI at 13.6 Gy with reduced lung exposure to 0.4 Gy by shielding, (iv) split-dose TBI at 12 Gy to twice per day over 4 days or (v) split-dose TBI at 12 Gy to twice per day over 4 days with reduced lung exposure to 0.36 Gy by shielding. The last radiation exposure preceded tail vein injection by 4-6 h. Mice were killed after 18 h. The homing of GFP-positive, lineage-negative cells was not significantly improved in any irradiated group compared with control. The homing of GFP-positive, lineage-negative, Kit-positive cells was significantly worse in all irradiated groups. TBI does not improve the homing of lineage-negative donor BM cells to the recipient marrow. The homing of lineage-negative, Kit-positive donor BM cells was significantly worse following TBI, with or without lung dose reduction.
Singh
A K
AK
Department of Radiation Medicine, Roswell Park Cancer Institute, Buffalo, NY 14263, USA anurag.singh@roswellpark.org
Chen
J
J
Calado
R
R
Sowers
A
A
Mitchell
J B
JB
Barrett
A J
AJ
D000818:Animals; D001853:Bone Marrow / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology* / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D008168:Lung / Q000528:radiation effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D014916:Whole-Body Irradiation