Developing Animal Models for Optimizing the Musculoskeletal Repair Potential of Emerging Human Progenitor Cell Therapies.

摘要

This 5 component award made significant advances to achieve most of the proposed objectives of the initial award. Most important was the demonstration that human marrow stromal cells are capable of making human bone in murine skeletal repair defects while commercial higher passage stromal preparations are ineffective in vivo. Human ES and induced pleuripotential cells can also produce bone and cartilage in vivo when grown under unique conditions prior to implantation. Standard mesenchymal culture condition do not preserve in vivo bone forming capability. A new source of adults stromal cells were identified in normal murine skeletal muscle that appear to be the initiator of heterotopic ossification. This cell source may have practical regenerative implication. Both weight bearing and growth factor releasing scaffold were evaluated in vivo to reveal properties that cannot be appreciated in vitro characterization studies. The importance of fixation rigidity became a central focus of our repair strategies, and image analysis programs that account for the changes in tissue dynamics during fracture repair were develop to access the effect of strategies that influence long bone healing. The method for achieving fixation rigidity had a major influence on the design of new long bone critical segmental defect models for both the mouse femur and tibia. The models are accepting of human cell engraftment and the fixation devices can be remove once the defect is closed to demonstrate both functional and mechanical competence.