Translational treatment paradigm for managing non-unions secondary to radiation injury utilizing adipose derived stem cells and angiogenic therapy.

BACKGROUND: Bony non-unions arising in the aftermath of collateral radiation injury are commonly managed with vascularized free tissue transfers. Unfortunately, these procedures are invasive and fraught with attendant morbidities. This study investigated a novel, alternative treatment paradigm utilizing adipose-derived stem cells (ASCs) combined with angiogenic deferoxamine (DFO) in the rat mandible. METHODS: Rats were exposed to a bioequivalent dose of radiation and mandibular osteotomy. Those exhibiting non-unions were subsequently treated with surgical debridement alone or debridement plus combination therapy. Radiographic and biomechanical outcomes were assessed after healing. RESULTS: Significant increases in biomechanical strength and radiographic metrics were observed in response to combination therapy (p < .05). Importantly, combined therapy enabled a 65% reduction in persisting non-unions when compared to debridement alone. CONCLUSION: We support the continued investigation of this promising combination therapy in its potential translation for the management of radiation-induced bony pathology. © 2015 Wiley Periodicals, Inc. Head Neck 38: E837-E843, 2016.

Prevention of radiation-induced bone pathology through combined pharmacologic cytoprotection and angiogenic stimulation.

Pathologic fractures and associated non-unions arising in previously irradiated bone are severely debilitating diseases. Although radiation is known to have deleterious effects on healthy tissue cellularity and vascularity, no clinically accepted pharmacologic interventions currently exist to target these destructive mechanisms within osseous tissues. We utilized amifostine-a cellular radioprotectant-and deferoxamine-an angiogenic stimulant-to simultaneously target the cellular and vascular niches within irradiated bone in a rat model of mandibular fracture repair following irradiation. Rats treated with combined therapy were compared to those undergoing treatment with singular amifostine or deferoxamine therapy, nontreated/irradiated animals (XFx) and non-treated/non-irradiated animals (Fx). 3D angiographic modeling, histology, Bone Mineral Density Distribution and mechanical metrics were utilized to assess therapeutic efficacy. We observed diminished metrics for all outcomes when comparing XFx to Fx alone, indicating the damaging effects of radiation. Across all outcomes, only the combined treatment group improved upon XFx levels, normalized all metrics to Fx levels, and was consistently as good as, or superior to the other treatment options (p<0.05). Collectively, our data demonstrate that pharmacologically targeting the cellular and vascular environments within irradiated bone prevents bone injury and enhances fracture healing.