Human bone marrow stromal cells display variable anatomic site-dependent response and recovery from irradiation.
OBJECTIVE
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.
Damek-Poprawa
Monika
M
Department of Oral Medicine, University of Pennsylvania, School of Dental Medicine, Philadelphia, PA 19104, United States.
Stefanik
Derek
D
Levin
Lawrence M
LM
Akintoye
Sunday O
SO
D000293:Adolescent; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*; D016026:Bone Marrow Transplantation / Q000502:physiology*; D001861:Bone Regeneration / Q000502:physiology*; D002453:Cell Cycle; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D002999:Clone Cells / Q000528:radiation effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis; D004249:DNA Damage; D020869:Gene Expression Profiling; D006801:Humans; D007085:Ilium / Q000166:cytology / Q000528:radiation effects; D007568:Jaw / Q000166:cytology* / Q000528:radiation effects; D016014:Linear Models; D011836:Radiation Tolerance / Q000235:genetics*; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016159:Tumor Suppressor Protein p53