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首页> 外文期刊>Biomolecular engineering >Clinical experience in cell-based therapeutics: disc chondrocyte transplantation A treatment for degenerated or damaged intervertebral disc.
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Clinical experience in cell-based therapeutics: disc chondrocyte transplantation A treatment for degenerated or damaged intervertebral disc.

机译：基于细胞的疗法的临床经验：椎间盘软骨细胞移植一种用于椎间盘退变或受损的治疗方法。

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Disc herniation treated by discectomy results in a significant loss of nucleus material and disc height. Biological restoration through the use of autologous disc chondrocyte transplantation offers a potential to achieve functional integration of disc metabolism and mechanics. Chondrocytes that have been removed from damaged cartilaginous tissues maintain a capacity to proliferate, produce and secrete matrix components and respond to physical stimuli such as dynamic loading. Nucleus regeneration using autologous cultured disc-derived chondrocytes (ADCT) has been demonstrated in a canine model and in clinical pilot studies. In 2002 a prospective, controlled, randomised, multi-center study, EuroDISC, comparing safety and efficacy of autologous disc chondrocyte transplant, chondrotransplant DISC, plus discectomy (ADCT), with discectomy alone was initiated. A dog model was used to investigate the hypothesis that autologous disc chondrocytes can be used to repair damaged intervertebral disc. Disc chondrocytes were harvested and expanded in culture under controlled and defined conditions, returned to the same animals from which they had been sampled (autologous transplantation) via percutaneous delivery. The animals were analyzed at specific times after transplantation by several methods to examine whether disc chondrocytes integrated with the surrounding tissue, produced the appropriate intervertebral disc extracellular matrix, and might provide a formative solution to disc repair. The clinical goals of the EuroDISC study, were to provide long-term pain relief, maintain disc height and prevent adjacent segment disease. Interim analysis was performed after 2 years; Oswestry (low back pain/disability), Quebec Back-Pain Disability Scale, as well as Prolo and VAS score were used for the evaluation. Disc height was assessed by MRI. In the context of degenerative changes in an injury model: () autologous disc chondrocytes were expended in culture and returned to the disc by a minimally invasive procedure after 12 weeks; () disc chondrocytes remained viable after transplantation as shown by bromodeoxyuridine incorporation and maintained a capacity for proliferation after transplantation as depicted by histology; () transplanted disc chondrocytes produced an extracellular matrix that displayed composition similar to normal intervertebral disc tissue. Positive evidence of Proteoglycan content was supported by accepted histochemical staining techniques such as Safranin O-Fast Green; () both Type II and Type I collagens were demonstrated in the regenerated intervertebral disc matrix by immunohistochemistry after chondrocyte transplantation; and () when the disc heights were analyzed for variance according to treatment a statistically significant-correlation between transplanting cells and retention of disc height was achieved. A clinically significant reduction of low back pain in the ADCT-treated group was shown by all three pain score systems. The median total Oswestry score was 2 in the ADCT-treated group compared with 6 in the control group. Decreases in the disability index and VAS score in ADCT-treated patients correlated strongly with the reduction of low back pain. Decreases in disc height over time were only found in the control group, and of potential significance, intervertebral discs in adjacent segments appeared to retain hydration when compared to those adjacent to levels that had undergone discectomy without cell intervention. Autologous chondrocyte transplantation is technically feasible and biologically relevant to repairing disc damage and retarding disc degeneration.
机译：经椎间盘切除术治疗的椎间盘突出症会导致髓核物质和椎间盘高度的大量损失。通过使用自体椎间盘软骨细胞移植进行生物修复提供了实现椎间盘代谢和力学功能整合的潜力。从受损的软骨组织中去除的软骨细胞具有增殖，产生和分泌基质成分并对物理刺激（例如动态负荷）作出反应的能力。在犬模型和临床试验研究中已经证明了使用自体培养的椎间盘源软骨细胞（ADCT）进行核再生。 2002年，进行了一项前瞻性，对照，随机，多中心研究，EuroDISC，比较了自体椎间盘软骨细胞移植，软骨移植DISC和椎间盘切除术（ADCT）与仅行椎间盘切除术的安全性和有效性。用狗模型研究了自体椎间盘软骨细胞可用于修复受损椎间盘的假说。收集椎间盘软骨细胞，并在控制和确定的条件下进行培养，然后通过经皮递送返回到与它们相同的动物中（自体移植）。在移植后的特定时间通过几种方法对动物进行分析，以检查椎间盘软骨细胞是否与周围组织整合，是否产生了合适的椎间盘间细胞外基质，并可能为椎间盘修复提供形成性解决方案。 EuroDISC研究的临床目标是提供长期的疼痛缓解，保持椎间盘高度并预防相邻节段疾病。两年后进行中期分析;评估采用Oswestry（下腰痛/残疾），魁北克背痛残疾量表以及Prolo和VAS评分。椎间盘高度通过MRI评估。在损伤模型发生退行性变化的情况下：（）将自体椎间盘软骨细胞用于培养，并在12周后通过微创手术将其返回椎间盘; （）圆盘软骨细胞在移植后如溴脱氧尿苷掺入所示保持存活，并在移植后如组织学所描绘的那样保持增殖能力; （）移植的椎间盘软骨细胞产生的细胞外基质显示出与正常椎间盘组织相似的组成。蛋白聚糖含量的阳性证据得到了公认的组织化学染色技术的支持，例如番红O-快速绿。 （）软骨细胞移植后通过免疫组织化学在再生的椎间盘基质中证实了II型和I型胶原。 （1）当根据治疗分析椎间盘高度的方差时，获得了移植细胞与椎间盘高度保留之间的统计学显着相关性。所有这三种疼痛评分系统均显示出ADCT治疗组的下背痛临床显着减轻。 ADCT治疗组的Oswestry总中位数为2，而对照组为6。 ADCT治疗的患者的残疾指数和VAS评分的降低与下腰痛的减少密切相关。仅在对照组中发现椎间盘高度随时间降低，并且具有潜在的意义，与那些未经细胞干预的椎间盘切除术相邻的椎间盘相比，相邻节段的椎间盘似乎保持了水合作用。自体软骨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有关。

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