Improving Soldier Recovery from Catastrophic Bone Injuries: Developing an Animal Model for Standarizing the Bone Reparative Potential of Emerging Progenitor Cell Therapies

摘要

During the first year of this award, we have demonstrated that mice carrying transgenic GFP reporters that reflect the level of osteoblast differentiation and the host/donor origin of these cells provides a rapid, highly informative and ultimately quantitative interpretation of a transplantation experiment of skeletal stem cells into a critical size bone defect. The calvarial defect model has been the primary platform to test a number of donor cell preparations and scaffold formulations. A combination of neonatal calvarial progenitors and a commercial scaffold achieves complete healing of the lesion occurs within in 3-4 months. Using this combination as a reference standard, we have begun to examine clinically relevant tissue sources and scaffolds with improved biomechanical properties that would be more appropriate for a long bone defect. To better understand the cellular basis of a long bone defect, we have utilized the GFP reporters in the closed tibial fracture. The surprise finding is the extent of activity of early vascular and skeletal progenitors that initiates well away from the fracture site and grows forward to form the callus. In the coming year we will apply the information learned from the calvarial defect to a non-union extension of the tibial fracture model.