Hohaus C, Ganey T M, Minkus Y, Meisel H J
Department of Neurosurgery, BG-Clinic Bergmannstrost, Halle, Germany.
Eur Spine J. 2008 Dec;17 Suppl 4(Suppl 4):492-503. doi: 10.1007/s00586-008-0750-6. Epub 2008 Nov 13.
Low back pain is an extremely common symptom, affecting nearly three-quarters of the population sometime in their life. Given that disc herniation is thought to be an extension of progressive disc degeneration that attends the normal aging process, seeking an effective therapy that staves off disc degeneration has been considered a logical attempt to reduce back pain. The most apparent cellular and biochemical changes attributable to degeneration include a decrease in cell density in the disc that is accompanied by a reduction in synthesis of cartilage-specific extracellular matrix components. With this in mind, one therapeutic strategy would be to replace, regenerate, or augment the intervertebral disc cell population, with a goal of correcting matrix insufficiencies and restoring normal segment biomechanics. Biological restoration through the use of autologous disc chondrocyte transplantation offers a potential to achieve functional integration of disc metabolism and mechanics. We designed an animal study using the dog as our model to investigate this hypothesis by transplantation of autologous disc-derived chondrocytes into degenerated intervertebral discs. As a result we demonstrated that disc cells remained viable after transplantation; transplanted disc cells produced an extracellular matrix that contained components similar to normal intervertebral disc tissue; a statistically significant correlation between transplanting cells and retention of disc height could displayed. Following these results the Euro Disc Randomized Trial was initiated to embrace a representative patient group with persistent symptoms that had not responded to conservative treatment where an indication for surgical treatment was given. In the interim analyses we evaluated that patients who received autologous disc cell transplantation had greater pain reduction at 2 years compared with patients who did not receive cells following their discectomy surgery and discs in patients that received cells demonstrated a significant difference as a group in the fluid content of their treated disc when compared to control. Autologous disc-derived cell transplantation is technically feasible and biologically relevant to repairing disc damage and retarding disc degeneration. Adipose tissue provides an alternative source of regenerative cells with little donor site morbidity. These regenerative cells are able to differentiate into a nucleus pulposus-like phenotype when exposed to environmental factors similar to disc, and offer the inherent advantage of availability without the need for transporting, culturing, and expanding the cells. In an effort to develop a clinical option for cell placement and assess the response of the cells to the post-surgical milieu, adipose-derived cells were collected, concentrated, and transplanted under fluoroscopic guidance directly into a surgically damaged disc using our dog model. This study provides evidence that cells harvested from adipose tissue might offer a reliable source of regenerative potential capable of bio-restitution.
腰痛是一种极为常见的症状,几乎四分之三的人在一生中的某个时候都会受到影响。鉴于椎间盘突出被认为是正常衰老过程中椎间盘进行性退变的延续,寻求一种能延缓椎间盘退变的有效疗法被视为减轻背痛的合理尝试。可归因于退变的最明显的细胞和生化变化包括椎间盘细胞密度降低,同时软骨特异性细胞外基质成分的合成减少。考虑到这一点,一种治疗策略是替代、再生或增加椎间盘细胞数量,目标是纠正基质不足并恢复正常节段生物力学。通过使用自体椎间盘软骨细胞移植进行生物修复,有可能实现椎间盘代谢和力学的功能整合。我们设计了一项以狗为模型的动物研究,通过将自体椎间盘来源的软骨细胞移植到退变的椎间盘中来研究这一假设。结果我们证明,移植后椎间盘细胞仍保持活力;移植的椎间盘细胞产生了一种细胞外基质,其所含成分与正常椎间盘组织相似;移植细胞与椎间盘高度保留之间存在统计学上的显著相关性。基于这些结果,启动了欧洲椎间盘随机试验,纳入了一组有代表性的患者,这些患者有持续症状且对保守治疗无反应,并有手术治疗指征。在中期分析中,我们评估发现,与椎间盘切除术后未接受细胞治疗的患者相比,接受自体椎间盘细胞移植的患者在2年后疼痛减轻更明显,并且接受细胞治疗的患者的治疗椎间盘的液体含量与对照组相比有显著差异。自体椎间盘来源的细胞移植在技术上是可行的,并且在生物学上与修复椎间盘损伤和延缓椎间盘退变相关。脂肪组织提供了一种再生细胞的替代来源,供体部位发病率很低。这些再生细胞在暴露于类似于椎间盘的环境因素时能够分化为髓核样表型,并且具有无需运输、培养和扩增细胞的固有优势,即可获得性。为了开发一种细胞植入的临床方案并评估细胞对术后环境的反应,我们使用狗模型收集、浓缩脂肪来源的细胞,并在荧光镜引导下直接将其移植到手术损伤的椎间盘中。这项研究提供了证据,表明从脂肪组织中获取的细胞可能提供一种可靠的具有生物修复潜力的再生来源。