The radiation protection and therapy effects of mesenchymal stem cells in mice with acute radiation injury.
The aim of this study was to investigate the effects and mechanisms of mesenchymal stem cells (MSCs) on haematopoietic reconstitution in reducing bone marrow cell apoptosis effects in irradiated mice, and to research the safe and effective dosage of MSCs in mice with total body irradiation (TBI). After BALB/c mice were irradiated with 5.5 Gy cobalt-60 gamma-rays, the following were observed: peripheral blood cell count, apoptosis rate, cell cycle, colony-forming unit-granulocyte macrophage (CFU-GM) and colony-forming unit-fibroblast (CFU-F) counts of bone marrow cells and pathological changes in the medulla. The survival of mice infused with three doses of MSCs after 8.0 Gy or 10 Gy TBI was examined. The blood cells recovered rapidly in the MSC groups. The apoptotic ratio of bone marrow cells in the control group was higher at 24 h after radiation. A lower ratio of G0/G1 cell cycle phases and a higher ratio of G2/M and S phases, as well as a greater number of haematopoietic islands and megalokaryocytes in the bone marrow, were observed in the MSC-treated groups. MSCs induced recovery of CFU-GM and CFU-GM and improved the survival of mice after 8 Gy TBI, but 1.5 x 10(8) kg(-1) of MSCs increased mortality. These results indicate that MSCs protected and treated irradiated mice by inducing haematopoiesis and reducing apoptosis. MSCs may be a succedaneous or intensive method of haematopoietic stem cell transplantation under certain radiation dosages, and could provide a valuable strategy for acute radiation syndrome.
Department of Haematology and Transplantation, Affiliated Hospital of Academy of Military Medical Sciences, Beijing, China.
K X
KX
Hu
Q Y
QY
Sun
M
M
Guo
H S
HS
Ai
D054508:Acute Radiation Syndrome / Q000628:therapy; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001854:Bone Marrow Cells / Q000473:pathology* / Q000528:radiation effects; D002453:Cell Cycle / Q000502:physiology / Q000528:radiation effects; D005260:Female; D006410:Hematopoiesis / Q000502:physiology* / Q000528:radiation effects; D007958:Leukocyte Count; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011829:Radiation Dosage; D011833:Radiation Injuries, Experimental / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D011835:Radiation Protection; D014916:Whole-Body Irradiation