Investigation of the Use of Bone Marrow Stem Cells to Facilitate Pathologic Fracture Healing of the Mandible After Irradiation
Alicia S. Snider, MD, Noah Nelson, BS, Alex Donneys, MD, Russell Ettinger, MD, Kavitha Ranganathan, MD, Alex Zheutlin, BS, Jose Rodriguez, MD, Steven Buchman, MD.
University of Michigan, Ann Arbor, MI, USA.
Purpose: Radiation therapy for head and neck cancer results in devastating morbidity for bone healing including the complications of osteoradionecrosis and subsequent pathologic fractures. Our investigation seeks to improve bone healing through the use of bone marrow stem cells (BMSCs) in a mandibular osteotomy defect following radiotherapy. Our hypothesis was that use of BMSCs would improve union rates and bone mineralization metrics thereby improving clinical outcomes
Methods: Lewis rats (n=31) were divided into 3 groups: non-radiated fracture (Fx), radiated fracture (XFx) and radiated fracture with BMSCs (XFxBMSC). The groups receiving radiation were administered a human-equivalent dose of 35Gy over 5 days. Two weeks later, the rats received a mandibular osteotomy and external fixation to 2.1mm. The animals were euthanized at post-operative day 40, their mandibles were harvested, examined for bony union, and μCT scanned. Metrics of bone mineral content, bone mineral density, tissue mineral content, tissue mineral density, and bone volume fraction were ascertained.
Results: While only 20% of the XFx group demonstrated unions, 66% of the XFxBMSC group had unions. For all mineralization metrics, a significant decrease was observed between Fx and XFx, and a significant remediation was imparted with BMSC therapy. Even more impressive was that no statistically significant differences were seen between the Fx and XFxBMSC groups.
Conclusion: BMSCs significantly improve the clinically relevant metrics of bony union and mineralization in a model of irradiated mandibular fracture healing. Given our results, we are proponents of additional studies in order to translate this promising therapy to clinical investigation.
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