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Stem Cells Int. 2015;2015:496512. doi: 10.1155/2015/496512. Epub 2015 May 5.

Particle Radiation-Induced Nontargeted Effects in Bone-Marrow-Derived Endothelial Progenitor Cells.

Author information

1
Cardiovascular Research Center, GeneSys Research Institute, Boston, MA 02135, USA.
2
Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA 02118, USA.
3
Department of Integrated Mathematical Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
4
Cardiovascular Research Center, GeneSys Research Institute, Boston, MA 02135, USA ; Tufts University School of Medicine, Boston, MA 02118, USA.
5
Cardiovascular Research Center, GeneSys Research Institute, Boston, MA 02135, USA ; Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA 02118, USA ; Tufts University School of Medicine, Boston, MA 02118, USA.

Abstract

Bone-marrow- (BM-) derived endothelial progenitor cells (EPCs) are critical for endothelial cell maintenance and repair. During future space exploration missions astronauts will be exposed to space irradiation (IR) composed of a spectrum of low-fluence protons ((1)H) and high charge and energy (HZE) nuclei (e.g., iron-(56)Fe) for extended time. How the space-type IR affects BM-EPCs is limited. In media transfer experiments in vitro we studied nontargeted effects induced by (1)H- and (56)Fe-IR conditioned medium (CM), which showed significant increase in the number of p-H2AX foci in nonirradiated EPCs between 2 and 24 h. A 2-15-fold increase in the levels of various cytokines and chemokines was observed in both types of IR-CM at 24 h. Ex vivo analysis of BM-EPCs from single, low-dose, full-body (1)H- and (56)Fe-IR mice demonstrated a cyclical (early 5-24 h and delayed 28 days) increase in apoptosis. This early increase in BM-EPC apoptosis may be the effect of direct IR exposure, whereas late increase in apoptosis could be a result of nontargeted effects (NTE) in the cells that were not traversed by IR directly. Identifying the role of specific cytokines responsible for IR-induced NTE and inhibiting such NTE may prevent long-term and cyclical loss of stem and progenitors cells in the BM milieu.

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