Biologic Solutions for Degenerative Disk Disease

Study Design: Literature review. Objective: Review the potential use of biologic therapies for the treatment of degenerative disk disease. Summary of Background Data: Degeneration of the intervertebral disk is a common occurrence which, although asymptomatic in most instances, may result in axial skeletal pain, radiculopathy, and myelopathy. Significant progress has been made in understanding the pathophysiology of degenerative disk disease and as a result, new biologic therapies, including molecular, gene, and cell-based strategies, are being investigated to halt and reverse disk degeneration. Results: Growth factors, inflammatory inhibitors, proteinase inhibitors, and intracellular regulatory proteins are among the molecular therapies that have been studied with encouraging results in both in vitro and in vivo experiments. However, the utility of these therapies in humans may be limited because of the limited therapeutic duration. Gene therapies have the potential to overcome the limited therapeutic duration of molecular treatments by transferring genes to the cells within the disk to encode for therapeutic proteins with potential long-term local production. Gene therapy for disk regeneration has been successful in a number of animal studies, but significant concerns exist with the safety of the many vectors used for gene transfer. Cell-based therapies, including reimplantation of nucleus pulposus cells expanded in culture and stem cell therapies, have also been studied extensively in animal models with good results. The EuroDisc clinical trial is currently underway in Europe exploring the reimplantation of disk cells that are removed at the time of diskectomy and expanded ex vivo. Mesenchymal stem cells, which are readily available without ethical concerns, are being studied extensively for disk regeneration. Mesenchymal stem cells can differentiate into a phenotype similar to native nucleus pulposus cells and have shown the potential for disk regeneration in animal studies. Conclusions: Biologic therapies for intervertebral disk regeneration have produced very encouraging results in both in vitro and in vivo studies. Despite successful experimental results, these therapies face a number of hurdles before acceptance for human use including safety concerns, efficacy in high-order animal and human studies, and issues with the role and timing of these treatments.