Gene-Augmented Mesenchymal Stem Cells in Bone Repair

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DESCRIPTION (provided by applicant): The healing of fractures involving bone and articular cartilage poses significant clinical challenge and socioeconomic impact. Numerous factors may impair healing of fractures, particularly those involving joints. It is estimated that 10-15% of 6.5 million fractures occurring annually will not heal. The elderly are more severely impacted and have greater morbidity associated with resulting osteoarthritis. Gene transfer in combination with bone marrow-derived mesenchymal stem cells (BMDMSC), which are pluripotent, can allow for controlled production of transgene products at desired sites, however, studies have not evaluated healing in fractures involving joints. Our goal is to identify the roles of bone morphogenetic proteins (BMPs) in BMDMSC during fracture healing, using an adenoviral delivery system. We will create an articular fracture in the distal femur of mice, implant BMP gene-transfected BMDMSC, and measure molecular signals associated with the rate and integrity of fracture repair. We hypothesize that gene delivery of two different BMPs will result in accelerated healing of fractures, but by different mechanisms, confirmed by the production of unique cartilage- and bone-specific messages.