Differential effect of ionizing radiation exposure on multipotent and differentiation-restricted bone marrow mesenchymal stem cells.
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.
Mussano
Federico
F
The Weintraub Center for Reconstructive Biotechnology, UCLA School of Dentistry, Los Angeles, California 90095, USA.
Lee
Kenneth J
KJ
Zuk
Patricia
P
Tran
Lisa
L
Cacalano
Nicholas A
NA
Jewett
Anahid
A
Carossa
Stefano
S
Nishimura
Ichiro
I
D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D001854:Bone Marrow Cells; D002454:Cell Differentiation; D004260:DNA Repair; D004307:Dose-Response Relationship, Radiation; D006657:Histones / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000528:radiation effects*; D051379:Mice; D039902:Multipotent Stem Cells / Q000528:radiation effects*; D011839:Radiation, Ionizing; D015854:Up-Regulation / Q000235:genetics
D051017:Apoptosis Regulatory Proteins; D006657:Histones; C475961:gamma-H2AX protein, mouse