Author/Authors :
Du, Y. Department of Pediatrics - Uniformed Services University of the Health Sciences, Bethesda, USA , Oakley, K. Department of Pediatrics - Uniformed Services University of the Health Sciences, Bethesda, USA , Han, Y. Department of Pediatrics - Uniformed Services University of the Health Sciences, Bethesda, USA , Banas, R.A. Noveome Biotherapeutics. Pittsburgh, USA , McCart, E.A. Department of Pharmacology - Uniformed Services University of the Health Sciences, Bethesda, USA , George, J. Department of Pharmacology - Uniformed Services University of the Health Sciences, Bethesda, USA , Day, R.M. Department of Pharmacology - Uniformed Services University of the Health Sciences, Bethesda, USA , Landauer, M.R. Armed Forces Radiobiology Research Institute - Uniformed Services University of the Health Sciences, Bethesda,, USA
Abstract :
Background: The hematopoietic system is sensitive to the adverse effects of ionizing radiation. Cellular therapies utilizing mesenchymal stem cells or vascular endothelial cells have been explored as potential countermeasures for radiation hematopoietic injuries. We investigated cells cultured from amnion (Amnion-derived Multipotent Progenitor cells, AMPs) for effects on hematopoietic recovery following total body irradiation in mice. Materials and Methods: C57BL/6J mice were sham-irradiated or exposed to 60Co irradiation (7.75 – 7.90 Gy, 0.6 Gy/min). Either AMPs (5 × 106 cells/animal) or vehicle were administered 24 h postirradiation via intraperitoneal injection. Results: We observed a 13% and 20% improvement in 30-day survival of mice treated with AMPs compared with treatment with vehicle following irradiation at 7.75 and 7.90 Gy, respectively. AMP treatment was characterized by a trend toward accelerated recovery of white blood cells, neutrophils, reticulocytes, and monocytes, measured through day 40 postirradiation after 7.75 Gy. AMP treatment enhanced hematopoietic cell repopulation of spleen and femoral bone marrow as measured by total nucleated cell and hematopoietic progenitor cell counts in comparison to vehicle-treated animals. FACS analysis showed that AMPs treatment significantly mitigated the reduction in CD11b+/Gr-1int and CD11b+/Gr-1high bone marrow cell populations at the nadir, and improved recovery of these cell types. Conclusion: Together, our data indicate that AMPs reduced hematopoietic toxicity induced by ionizing radiation when infused within 24 h after radiation injury.
Keywords :
adult stem cells , acute radiation syndrome , ionizing radiation , radiation countermeasure , hematopoietic progenitor
