Date of this Version
Archives of Oral Biology
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.
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.
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.
Effect of irradiation on human BMSCs was skeletal site-specific with OF-MSCs displaying higher radio-resistance and quicker recovery than IC-MSCs.
This manuscript version is made available under the CC-BY-NC-ND 4.0 license
bone marrow stromal cells, bone regeneration, osteoradionecrosisIonizing, radiation, jaws
Damek-Poprawa, M., Stefanik, D., Levin, L., & Akintoye, S. O. (2010). Human Bone Marrow Stromal Cells Display Variable Anatomic Site-Dependent Response and Recovery From Irradiation. Archives of Oral Biology, 55 (5), 358-364. http://dx.doi.org/10.1016/j.archoralbio.2010.03.010
Date Posted: 10 August 2018
This document has been peer reviewed.