背景:腰椎间盘突出症(IVD)与严重的残疾有关。椎间盘切除术是IVD疝的常规治疗选择,但会导致IVD缺损,自我修复能力低,从而代表进一步IVD变性的风险。无细胞,生物可吸收,和良好的生产规范(GMP)-符合原位形成凝胶,它可以纠正椎间盘切除术相关的IVD缺损,并防止IVD进一步变性。然而,这种基于脱细胞基质的策略有一定的局限性,尤其是老年患者,其组织具有较低的自我修复能力。这项研究的目的是研究使用新开发的组合的治疗效果,超纯化,符合GMP标准,在严重IVD变性的绵羊模型中,椎间盘切除术后人骨髓间充质干细胞(快速扩增的克隆;RECs)和IVD再生凝胶。
方法:将RECs和髓核细胞(NPCs)在凝胶中共培养。此外,在具有退化的IVD的绵羊的椎间盘切除术后,将与凝胶结合的RECs植入IVD。
结果:NPC标记的基因表达,生长因子,与每种单一培养物相比,共培养物中的细胞外基质显着增加。REC和凝胶组合在严重IVD变性绵羊模型中增强椎间盘切除术后(长达24周)的IVD再生。
结论:这些发现证明了RECs与原位形成凝胶的组合用于治疗退行性人IVD中的疝的翻译潜力。
背景:教育部,文化,体育,科学,和日本的技术,日本医学研究开发机构,和Mochida制药公司,Ltd.
BACKGROUND: Lumbar intervertebral disc (IVD) herniations are associated with significant disability. Discectomy is the conventional treatment option for IVD herniations but causes a defect in the IVD, which has low self-repair ability, thereby representing a risk of further IVD degeneration. An acellular, bioresorbable, and good manufacturing practice (GMP)-compliant in situ-forming gel, which corrects discectomy-associated IVD defects and prevents further IVD degeneration had been developed. However, this acellular matrix-based strategy has certain limitations, particularly in elderly patients, whose tissues have low self-repair ability. The aim of this study was to investigate the therapeutic efficacy of using a combination of newly-developed, ultra-purified, GMP-compliant, human bone marrow mesenchymal stem cells (rapidly expanding clones; RECs) and the gel for IVD regeneration after discectomy in a sheep model of severe IVD degeneration.
METHODS: RECs and nucleus pulposus cells (NPCs) were co-cultured in the gel. In addition, RECs combined with the gel were implanted into IVDs following discectomy in sheep with degenerated IVDs.
RESULTS: Gene expression of NPC markers, growth factors, and extracellular matrix increased significantly in the co-culture compared to that in each mono-culture. The REC and gel combination enhanced IVD regeneration after discectomy (up to 24 weeks) in the severe IVD degeneration sheep model.
CONCLUSIONS: These findings demonstrate the translational potential of the combination of RECs with an in situ-forming gel for the treatment of herniations in degenerative human IVDs.
BACKGROUND: Ministry of Education, Culture, Sports, Science, and Technology of Japan, Japan Agency for Medical Research and Development, and the Mochida Pharmaceutical Co., Ltd.