August 29, 2005
Adult stem cells come in many varieties, but none hold greater promise than muscle-derived stem cells, or MDSCs, to heal bone fractures and/or repair severe craniofacial wounds. These cells can be readily harvested from the skeletal muscles and genetically engineered in the laboratory to produce bone-forming osteoblasts. Preliminary work with rodents demonstrates that these genetically engineered MDSCs will produce ample amounts of bone-forming cells when implanted into large skull wounds. The big challenge facing researchers is to learn how to best engineer the MDSCs at the front end, and thus optimize the ensuing bone formation. That, in part, entails learning which combinations of genes to transfer into the MDSCs in the laboratory to mimic the natural response that occurs during fracture healing. In the August issue of the journal Molecular Therapy, NIDCR grantees and colleagues report results from mouse studies that constitute a major step in this direction. They tested the hypothesis that transferring the pro-growth bone morphogenetic protein 4 (BMP4) and its biochemical nemesis, or antagonist, called Noggin, would provide a more dynamic, stop-and-go healing process to repair large skull wounds. That's precisely what they found. The combination of genes whose proteins act concurrently and interactively in nature to form bone prevented resting levels of unwanted bone regeneration and overgrowth, but, more importantly, generated bone that more closely resembled normal bone. The authors concluded, "We believe that this regulatable tissue engineering strategy, enhanced by utilizing a specific antagonist, constitutes a new paradigm for tissue engineering and regenerative medicine."