Mesenchymal stem cell and gene therapies for spinal fusion

Abstract

THE IDEAL GRAFT material to promote spinal fusion should possess osteoconductive, osteoinductive, and osteogenic properties. Although autogenous bone graft has all three qualities and is the standard for comparison, research has focused on finding alternatives that have similar efficacy but not the morbidities associated with graft donor sites. Efforts have focused on various osteoconductive scaffolds and introduction of osteoinductive proteins, including bone morphogenetic protein. Recently, interest in using osteoprogenitor cells, or osteogenesis, for spinal fusion has increased. Bone marrow aspiration allows the introduction of mesenchymal stem cells and ultimately osteoblasts to promote fusion. Preclinical studies suggest that the addition of osteoprogenitor cells to various osteoconductive materials results in a fusion rate similar to that of autograft. There is growing recognition that local gene therapy has the benefit of delivering therapeutic genes that encode novel osteoinductive proteins. Gene delivery offers an alternative to local implantation of recombinant protein, which typically requires high doses of the protein to result in a sufficient osteoinductive response. The findings of animal studies demonstrate that gene therapy results in sustained and regulated production of desired osteoinductive proteins and is efficacious in promoting spinal fusion; however, before treatment in humans can be undertaken, obstacles such as the safety profile, host immune response, transfection rates with insufficient transgene expression, and imprecise control of the timing of transgene expression must be overcome. In this review, the authors summarize the latest research efforts under way to promote spinal fusion with osteoprogenitor cells and gene therapy and discuss the clinical implications of these treatments.