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Differential effect of ionizing radiation exposure on multipotent and differentiation‐restricted bone marrow mesenchymal stem cells
Author(s) -
Mussano Federico,
Lee Kenneth J.,
Zuk Patricia,
Tran Lisa,
Cacalano Nicholas A.,
Jewett Anahid,
Carossa Stefano,
Nishimura Ichiro
Publication year - 2010
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.22699
Subject(s) - mesenchymal stem cell , bone marrow , radioresistance , stem cell , cancer research , multipotent stem cell , ionizing radiation , haematopoiesis , biology , chemistry , microbiology and biotechnology , immunology , progenitor cell , irradiation , cell culture , genetics , physics , nuclear physics
Debilitating effects of bone marrow from ionizing radiation exposure has been well established for hematopoietic stem cells; however, radiation toxicity of mesenchymal stem cells (MSCs) has been controversial. The present study addressed if ionizing radiation exposure differently affected bone marrow MSCs with various differentiation commitments. Mouse bone‐marrow‐derived MSCs, D1 cells of early passages (≤5 passages; p5) maintained the complete characteristics of multipotent MSCs, whereas, after ≥45 passages (p45) the differentiation capability of D1 cells became partially restricted. Both p5 and p45 D1 cells were subjected to single dose irradiation by radioactive isotope 137 Cs. Radiation treatment impaired cell renewal and differentiation activities of p5 D1 cells; however, p45 D1 cells were less affected. Radiation treatment upregulated both pro‐ and anti‐apoptotic genes of p5 D1 cells in a dose‐dependent manner, potentially resulting in the various apoptosis thresholds. It was found that constitutive as well as radiation‐induced phosphorylation levels of histone H2AX was significantly higher in p45 D1 cells than in p5 D1 cells. The increased repair activity of DNA double‐strand breakage may play a role for p45 D1 cells to exhibit the relative radioresistance. In conclusion, the radiation toxicity predominantly affecting multipotent MSCs may occur at unexpectedly low doses, which may, in part, contribute to the catabolic pathology of bone tissue. J. Cell. Biochem. 111: 322–332, 2010. © 2010 Wiley‐Liss, Inc.