Intervertebral Disk Transplantation

With aging, the nucleus pulposus of the intervertebral disk begins to desiccate, characterized by a loss of aggrecan core proteins, glycosaminoglycan, matrix turnover, and cell numbers that eventually leads to losing the ability to imbibe water. As the nucleus pulposus loses its water content, the disk can no longer distribute forces effectively. The annulus fibrosus buckles under compressive loading, and this leads to disk collapse. Further load on the annulus fibrosus leads to fissuring and cracks. Loss of disk height also leads to overriding facet joints. Uneven loading causes osteophyte formation and joint instability. Pain associated with intervertebral disk degeneration can be caused by bulging or rupturing of the annulus with herniation of disk material irritating the pain fibers in the peripheral part of the annulus. Neural tissues are also implicated in herniated disks as a result of mechanical or chemical irritation. Finally, degenerated facet joints, together with instability, subluxation, or deformity of the functional spinal unit (FSU), can also produce pain.

If conservative modalities fail, surgical intervention is indicated, especially in those patients with significant neurologic compromise. Classically, the most common surgical treatment for lumbar disk degeneration is spinal fusion. Although effective in controlling pain, fusion leads to restriction of the spinal motion and may cause adjacent level degeneration secondary to increased stress and motion at adjacent levels. The goals of surgical treatment of lumbar spine degeneration are to relieve any neural compression and to maintain a stable FSU that is free of deformity. Thus, many different types of intervertebral disk implants have been advocated to avoid the effects of spinal fusion and to preserve motion. Artificial disks made of metals, polymers, or combinations of materials have been attempted and are gaining popularity. The early results of total disk replacement (TDR) are encouraging and are at least comparable to the results of spinal fusion. However, questions have been raised regarding the implant material, design kinematics, recipient factors, surgical precision, and long-term outcome and salvage options. An interesting long-term study of artificial disk replacement showed that the best results occurred in patients who had spontaneous fusion in the replaced disk.

Disk replacements can also be biologic, with the goals of preserving anatomy, motion, and stability. Theoretically, one could manufacture a disk scaffold using tissue engineering technology. Appropriate cells with necessary promoter growth factors can be used to populate this scaffold. Regeneration or repair of the disk by using growth factors, gene therapy, and cell therapy is being actively researched. Most experiments are focused on the rejuvenation of the nucleus pulposus by restoring the matrix production through increasing cell numbers. However, this approach has a major flaw because the annulus fibrosus is also structurally and mechanically incompetent when the disk is degenerated to the point of causing symptoms. In addition, the delivery channel in which nutrients reach the disk is also jeopardized. This limits sustained cell viability and the ability for cells to restore the matrix or to repair the damaged annulus fibrosus. Current evidence suggests that cellular therapy is unable to restore the matrix content in advanced disk degeneration but can only maintain it in mild degeneration.

The concept of disk transplantation began in 1991 when Olson and associates reconstructed a spinal column defect by using a quadruped model transplantation of a vertebral body together with the two adjacent disks to act as a spacer. Relatively normal mobility and stability of the spinal column were found because of partial revascularization of the intervening vertebral body and the intervertebral disks. The same research group followed up with a fresh autograft disk transfer in a canine model. In this experiment, the morphology and the metabolic functions of the transplanted disks were abnormal, but the structure and function were maintained. The likely cause of these findings was attributed to the rigidly fixed transplanted disks, which jeopardized disk nutrition. Further studies by Katsuura and Hukuda, as well as by Matsuzaki and colleagues, used cryopreserved allografts in quadruped models, but these investigators experienced the same limitation of rigid fixation of the grafts with plates and screws.

Around the same time as the study by Olson and colleagues, Professor Keith DK Luk and investigators at the Department of Orthopaedics and Traumatology at the University of Hong Kong had a similar idea of disk transplantation that avoided constraining the transplanted graft. Experiments were conducted in upright primates, the model closest to human biomechanics. A series of experiments was performed to verify this animal model, disk autograft, disk allograft, and fresh frozen allograft. Further studies were carried out to validate the storage processing technique and implantation technique. A small-scale clinical trial was conducted in 2000 to prove the applicability of this technique in clinical practice. The following discussion provides an account of the evolution of allograft disk transplantation from animal models to the latest clinical trial outcomes, as based on the experience of investigators at the University of Hong Kong and their collaborators.