1. Human bone marrow stromal cells display variable anatomic site-dependent response and recovery from irradiation.
- Author
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Damek-Poprawa M, Stefanik D, Levin LM, and Akintoye SO
- Subjects
- Adolescent, Apoptosis, Bone Marrow Cells cytology, Bone Marrow Cells metabolism, Cell Cycle, Cell Differentiation, Cell Proliferation, Cell Survival, Cells, Cultured, Clone Cells radiation effects, Cyclin-Dependent Kinase Inhibitor p21 biosynthesis, DNA Damage, Gene Expression Profiling, Humans, Ilium cytology, Ilium radiation effects, Jaw radiation effects, Linear Models, Stromal Cells cytology, Stromal Cells metabolism, Tumor Suppressor Protein p53 physiology, Bone Marrow Cells radiation effects, Bone Marrow Transplantation physiology, Bone Regeneration physiology, Jaw cytology, Radiation Tolerance genetics, Stromal Cells radiation effects
- Abstract
Objectives: Orofacial bone is commonly affected by osteoradionecrosis (ORN) during head and neck cancer radiotherapy possibly due to interactions of several factors including radiation damage to resident bone marrow stromal cells (BMSCs). Irradiation causes DNA damage, triggers p53-dependent signalling resulting in either cell-cycle arrest or apoptosis. In same individuals, disproportionately higher rapid growth of orofacial BMSCs relative to those of axial/appendicular bones suggests their response to radiation is skeletally site-specific. We hypothesised that survival and osteogenic recovery capacity of irradiated human BMSCs is site-dependent based on anatomic skeletal site of origin., Methods: Early passage BMSCs from maxilla, mandible and iliac crest of four normal volunteers were exposed to 2.5 to 10 Gy gamma radiation to evaluate clonogenic survival, effects on cell cycle, DNA damage, p53-related response and in vivo osteogenic regenerative capacity., Results: Orofacial bone marrow stromal cells (OF-MSCs) survived higher radiation doses and recovered quicker than iliac crest (IC-MSCs) based on clonogenic survival, proliferation and accumulation in G0G1 phase. Post-irradiation p53 level was relatively unchanged but expression of p21, a downstream effector was moderately increased in OF-MSCs. Re-establishment of in vivo bone regeneration was delayed more in irradiated IC-MSCs relative to OF-MSCs., Conclusions: Effect of irradiation on human BMSCs was skeletal site-specific with OF-MSCs displaying higher radio-resistance and quicker recovery than IC-MSCs., (Copyright 2010 Elsevier Ltd. All rights reserved.)
- Published
- 2010
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