造血
生物
骨髓
旁观者效应
干细胞
间质细胞
免疫学
间充质干细胞
癌症研究
细胞生物学
造血干细胞
作者
Graça Almeida-Porada,Christopher Rodman,Bradford Mitchell Kuhlman,Egil Brudvik,John H. Moon,Sunil George,Peter Guida,Satria Sajuthi,Carl D. Langefeld,Stephen J. Walker,Paul F. Wilson,Christopher D. Porada
出处
期刊:Stem Cells and Development
[Mary Ann Liebert]
日期:2018-09-15
卷期号:27 (18): 1237-1256
被引量:16
标识
DOI:10.1089/scd.2018.0005
摘要
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 hematopoietic stem cells (HSC) to simulated solar energetic particle (SEP) and galactic cosmic ray (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 this study, we performed the first in-depth examination to define changes that occur in mesenchymal stem cells present in the human BM niche following exposure to accelerated protons and iron ions and assess the impact these changes have upon human hematopoiesis. Our data provide 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.
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