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

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 (1H) and high charge and energy (HZE) n...

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Main Authors: Sharath P. Sasi, Daniel Park, Sujatha Muralidharan, Justin Wage, Albert Kiladjian, Jillian Onufrak, Heiko Enderling, Xinhua Yan, David A. Goukassian
Format: Article
Language:English
Published: Wiley 2015-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2015/496512
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author Sharath P. Sasi
Daniel Park
Sujatha Muralidharan
Justin Wage
Albert Kiladjian
Jillian Onufrak
Heiko Enderling
Xinhua Yan
David A. Goukassian
author_facet Sharath P. Sasi
Daniel Park
Sujatha Muralidharan
Justin Wage
Albert Kiladjian
Jillian Onufrak
Heiko Enderling
Xinhua Yan
David A. Goukassian
author_sort Sharath P. Sasi
collection DOAJ
description 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 (1H) and high charge and energy (HZE) nuclei (e.g., iron-56Fe) 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 1H- and 56Fe-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 1H- and 56Fe-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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spelling doaj-art-a9b40395e5fb481fb27737d8207d59fe2025-08-20T03:39:10ZengWileyStem Cells International1687-966X1687-96782015-01-01201510.1155/2015/496512496512Particle Radiation-Induced Nontargeted Effects in Bone-Marrow-Derived Endothelial Progenitor CellsSharath P. Sasi0Daniel Park1Sujatha Muralidharan2Justin Wage3Albert Kiladjian4Jillian Onufrak5Heiko Enderling6Xinhua Yan7David A. Goukassian8Cardiovascular Research Center, GeneSys Research Institute, Boston, MA 02135, USACardiovascular Research Center, GeneSys Research Institute, Boston, MA 02135, USAWhitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA 02118, USACardiovascular Research Center, GeneSys Research Institute, Boston, MA 02135, USACardiovascular Research Center, GeneSys Research Institute, Boston, MA 02135, USACardiovascular Research Center, GeneSys Research Institute, Boston, MA 02135, USADepartment of Integrated Mathematical Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USACardiovascular Research Center, GeneSys Research Institute, Boston, MA 02135, USACardiovascular Research Center, GeneSys Research Institute, Boston, MA 02135, USABone-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 (1H) and high charge and energy (HZE) nuclei (e.g., iron-56Fe) 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 1H- and 56Fe-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 1H- and 56Fe-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.http://dx.doi.org/10.1155/2015/496512
spellingShingle Sharath P. Sasi
Daniel Park
Sujatha Muralidharan
Justin Wage
Albert Kiladjian
Jillian Onufrak
Heiko Enderling
Xinhua Yan
David A. Goukassian
Particle Radiation-Induced Nontargeted Effects in Bone-Marrow-Derived Endothelial Progenitor Cells
Stem Cells International
title Particle Radiation-Induced Nontargeted Effects in Bone-Marrow-Derived Endothelial Progenitor Cells
title_full Particle Radiation-Induced Nontargeted Effects in Bone-Marrow-Derived Endothelial Progenitor Cells
title_fullStr Particle Radiation-Induced Nontargeted Effects in Bone-Marrow-Derived Endothelial Progenitor Cells
title_full_unstemmed Particle Radiation-Induced Nontargeted Effects in Bone-Marrow-Derived Endothelial Progenitor Cells
title_short Particle Radiation-Induced Nontargeted Effects in Bone-Marrow-Derived Endothelial Progenitor Cells
title_sort particle radiation induced nontargeted effects in bone marrow derived endothelial progenitor cells
url http://dx.doi.org/10.1155/2015/496512
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