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Title: Exposure of the Bone Marrow Microenvironment to Simulated Solar and Galactic Cosmic Radiation Induces Biological Bystander Effects on Human Hematopoiesis

Abstract

The stem cell compartment of the hematopoietic system constitutes one of the most radiosensitive tissues of the body and leukemias represent one of the most frequent radiogenic cancers with short latency periods. As such, leukemias may pose a particular threat to astronauts during prolonged space missions. Control of hematopoiesis is tightly governed by a specialized bone marrow (BM) microenvironment/niche. As such, any environmental insult that damages cells of this niche would be expected to produce pronounced effects on the types and functionality of hematopoietic/immune cells generated. We recently reported that direct exposure of human HSC to simulated SEP and GCR radiation dramatically altered the differentiative potential of these cells, and that simulated GCR exposures can directly induce DNA damage and mutations within human HSC, which led to leukemic transformation when these cells repopulated murine recipients. In the present study, we performed the first in depth examination to define changes that occur in mesenchymal stem cells (MSC) present in the human BM niche following exposure to accelerated protons and iron ions, and assess the impact these changes have upon human hematopoiesis. Here, our data thus provides compelling evidence that simulated SEP/GCR exposures can also contribute to defective hematopoiesis/immunity through so-called “biologicalmore » bystander effects” by damaging the stromal cells that comprise the human marrow microenvironment, thereby altering their ability to support normal hematopoiesis.« less

Authors:
 [1];  [1];  [1];  [1];  [1];  [1];  [2];  [3];  [3];  [1];  [4];  [1]
  1. Wake Forest Univ., Winston-Salem, NC (United States). School of Medicine and Inst. for Regenerative Medicine
  2. Brookhaven National Lab. (BNL), Upton, NY (United States). Biological, Environmental, and Climate Sciences Dept.
  3. Wake Forest Univ., Winston-Salem, NC (United States). Center for Public Health Genomics and Dept. of Biostatistical Sciences and Division of Public Health Sciences
  4. Univ. of California, Davis, CA (United States). Comprehensive Cancer Center and Dept. of Radiation Oncology
Publication Date:
Research Org.:
Brookhaven National Laboratory (BNL), Upton, NY (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)
OSTI Identifier:
1430862
Report Number(s):
BNL-203398-2018-JAAM
Journal ID: ISSN 1547-3287
Grant/Contract Number:
SC0012704; NNX13AB67G; NNX17AE49G
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Stem Cells and Development
Additional Journal Information:
Journal Name: Stem Cells and Development; Journal ID: ISSN 1547-3287
Publisher:
Mary Ann Liebert, Inc.
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 79 ASTRONOMY AND ASTROPHYSICS; Bone Marrow; Hematopoiesi; MSC

Citation Formats

Almeida-Porada, Graca, Rodman, Christopher, Kuhlman, Bradford, Brudvik, Egil, Moon, John, George, Sunil, Guida, Peter, Sajuthi, Satria, Langefeld, Carl, Walker, Stephen, Wilson, Paul, and Porada, Christopher. Exposure of the Bone Marrow Microenvironment to Simulated Solar and Galactic Cosmic Radiation Induces Biological Bystander Effects on Human Hematopoiesis. United States: N. p., 2018. Web. doi:10.1089/scd.2018.0005.
Almeida-Porada, Graca, Rodman, Christopher, Kuhlman, Bradford, Brudvik, Egil, Moon, John, George, Sunil, Guida, Peter, Sajuthi, Satria, Langefeld, Carl, Walker, Stephen, Wilson, Paul, & Porada, Christopher. Exposure of the Bone Marrow Microenvironment to Simulated Solar and Galactic Cosmic Radiation Induces Biological Bystander Effects on Human Hematopoiesis. United States. doi:10.1089/scd.2018.0005.
Almeida-Porada, Graca, Rodman, Christopher, Kuhlman, Bradford, Brudvik, Egil, Moon, John, George, Sunil, Guida, Peter, Sajuthi, Satria, Langefeld, Carl, Walker, Stephen, Wilson, Paul, and Porada, Christopher. Thu . "Exposure of the Bone Marrow Microenvironment to Simulated Solar and Galactic Cosmic Radiation Induces Biological Bystander Effects on Human Hematopoiesis". United States. doi:10.1089/scd.2018.0005.
@article{osti_1430862,
title = {Exposure of the Bone Marrow Microenvironment to Simulated Solar and Galactic Cosmic Radiation Induces Biological Bystander Effects on Human Hematopoiesis},
author = {Almeida-Porada, Graca and Rodman, Christopher and Kuhlman, Bradford and Brudvik, Egil and Moon, John and George, Sunil and Guida, Peter and Sajuthi, Satria and Langefeld, Carl and Walker, Stephen and Wilson, Paul and Porada, Christopher},
abstractNote = {The stem cell compartment of the hematopoietic system constitutes one of the most radiosensitive tissues of the body and leukemias represent one of the most frequent radiogenic cancers with short latency periods. As such, leukemias may pose a particular threat to astronauts during prolonged space missions. Control of hematopoiesis is tightly governed by a specialized bone marrow (BM) microenvironment/niche. As such, any environmental insult that damages cells of this niche would be expected to produce pronounced effects on the types and functionality of hematopoietic/immune cells generated. We recently reported that direct exposure of human HSC to simulated SEP and GCR radiation dramatically altered the differentiative potential of these cells, and that simulated GCR exposures can directly induce DNA damage and mutations within human HSC, which led to leukemic transformation when these cells repopulated murine recipients. In the present study, we performed the first in depth examination to define changes that occur in mesenchymal stem cells (MSC) present in the human BM niche following exposure to accelerated protons and iron ions, and assess the impact these changes have upon human hematopoiesis. Here, our data thus provides compelling evidence that simulated SEP/GCR exposures can also contribute to defective hematopoiesis/immunity through so-called “biological bystander effects” by damaging the stromal cells that comprise the human marrow microenvironment, thereby altering their ability to support normal hematopoiesis.},
doi = {10.1089/scd.2018.0005},
journal = {Stem Cells and Development},
number = ,
volume = ,
place = {United States},
year = {Thu Apr 26 00:00:00 EDT 2018},
month = {Thu Apr 26 00:00:00 EDT 2018}
}

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