Systemically administered MSCs given 24hrs after osteotomy do not affect bone formation in rat distraction osteogenesis

Abstract

Distraction osteogenesis is a unique postnatal bone formation employed by orthopaedic surgeons to treat many conditions, however, the overall time to external frame removal can be extensive. Any strategies that accelerate healing would improve patient care. Distraction osteogenesis research in the past decade has shown that direct stem cell implantation enhances new bone formation. Systemic implantation would be more clinically desirable. Systemically delivered stem cells have been shown to home to a mandibular distraction site; however, effects on bone formation have not been studied. Ten-week-old, male Sprague-Dawley rats underwent surgery to implant an external fixator-distractor and an osteotomy was performed. Twenty-four hours postoperatively, each rat received tail vein injections of either saline or 10^6 fluorescently labeled primary mesenchymal stem cells. Animals in the validation groups were euthanized two days after surgery and the femora processed for histology. Animals in the experimental groups were given five days of latency, then the femur was lengthened once daily for five days (0.75mm/day, 3.75mm total). Following four weeks of consolidation, the animals were euthanized and the femora were evaluated by microCT and histology to quantify new bone formation. Labeled stem cells were found at the distraction site in validation animals. However, there were no differences in any bone or soft tissue outcomes. Systemic stem cell administration 24 hours after surgery does not improve DO outcomes. It is possible that the animal model was not challenging enough to discriminate any augmentation provided by stem cells.