Gene therapy for spinal fusion.
ABSTRACT Spinal fusion will continue to be an important part of the surgical treatment of spinal pathology for the foreseeable future. Traditional challenges to successful spinal fusion surgery include autograft donor site morbidity and pseudoarthrosis. Recent advances in the understanding of the biology of bone formation have allowed the development of therapeutic biologics. Although recombinant bone morphogenetic proteins delivered to the arthrodesis site will stimulate fusion, these proteins have been less successful in more challenging fusion situations (posterolateral), require supraphysiologic doses to promote fusion in humans, and are quite expensive. Gene therapy may represent the easiest method for the application of bone-forming biologic agents to promote spinal fusion. Both in vivo and ex vivo techniques of delivery of therapeutic genes have been used effectively to promote fusion in lower animals. Considerable research is required to identify gene therapy techniques and vectors with acceptable safety profiles and high fusion rates.
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ABSTRACT: In impaction grafting for revision joint arthroplasty, the morselized cancellous bone ideally remodels into a new contiguous lattice. However, the use of biologically active factors may sometimes be indicated to enhance fusion. The purpose of this study was to determine the stability of femoral impaction-graft constructs for which either only the proximal or distal half of the morselized cancellous bone volume was modeled as fused. Fusing the proximal half of the impaction-graft volume resulted in a higher femoral stem stability than did fusing the distal half. This proximal graft fusion also resulted in a stem stability that was similar to that of fusing the entire graft. These results emphasize the importance of proximal fixation of an impaction-grafted femoral stem.The Journal of arthroplasty 02/2008; 23(6):921-6. DOI:10.1016/j.arth.2007.08.006 · 2.37 Impact Factor
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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.Neurosurgery 10/2008; 63(3):380-91; discussion 391-2. DOI:10.1227/01.NEU.0000324990.04818.13 · 3.03 Impact Factor
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ABSTRACT: Anterior cervical discectomy with fusion is a common surgical procedure for patients suffering pain and/or neurological deficits and unresponsive to conservative management. For decades, autologous bone grafted from the iliac crest has been used as a substrate for cervical arthrodesis. However patient dissatisfaction with donor site morbidity has led to the search for alternative techniques. We present a literature review examining the progress of available grafting options as assessed in human clinical trials, considering allograft-based, synthetic, factor- and cell-based technologies.European Spine Journal 04/2009; 18(4):449-464. DOI:10.1007/s00586-008-0878-4 · 2.47 Impact Factor