Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Acta Biomater. 2019 Mar 15;87:118-129. doi: 10.1016/j.actbio.2019.01.050. Epub 2019 Jan 25.
Low back pain results in more global disabilities than any other condition, and intervertebral disc (IVD) degeneration is commonly involved in the etiology. Supplementation of IVDs with reparative cells is a rational strategy to address such clinical problems. We have previously developed a scaffold-free tissue-engineered construct (TEC) as a novel cell therapy system for repair of articular cartilage and meniscus. We now show the regenerative potential of adipose mesenchymal stem cells derived TEC (ADSC-TEC) for IVD degeneration using a rat tail model of total nucleotomy. The regenerative efficacy of ASDC-TEC was investigated structurally and biomechanically up to 6 months after implantation. ADSC-TEC implantation into IVDs preserved the disc height, endplate, and annulus fibrosus structure, and showed similar biomechanical characteristics to the sham group at postoperative 6 weeks. The structure of regenerated IVD was maintained until 6 months. Furthermore, ADSC-TEC implantation attenuated the impact of age-related biomechanical deterioration when assessed at 6 months post-implantation. These results demonstrate that use of ADSC-TECs can be an effective treatment for IVD degeneration. STATEMENT OF SIGNIFICANCE: We developed adipose mesenchymal stem cell-derived scaffold-free tissue engineered construct (ADSC-TEC) as a novel cell therapy system. The ADSC-TEC implantation into a rat total-nucleotomized disc space regenerated intervertebral discs (IVDs) histologically and biomechanically. The regenerative capacity of the ADSC-TEC was exerted by its trophic effects on annulus fibrosus cells and the load-sharing effect at intervertebral space. Interestingly, the regenerated IVDs by the ADSC-TEC was less susceptible to the age-related deterioration than the IVDs of normal rats. Thus, the application of ADSC-TEC into the degenerated disc can be an alternative therapy for various disease associated with structural and functional failure of IVDs.
腰痛导致的全球残疾比任何其他疾病都多，而椎间盘（IVD）退变通常与病因有关。用修复细胞补充 IVD 是解决此类临床问题的合理策略。我们之前开发了一种无支架组织工程构建体（TEC），作为一种新型细胞治疗系统，用于修复关节软骨和半月板。我们现在展示了脂肪间充质干细胞衍生的 TEC（ADSC-TEC）在全核切除大鼠模型中对 IVD 退变的再生潜力。在植入后长达 6 个月的时间里，从结构和生物力学两方面研究了 ADSC-TEC 的再生效果。ADSC-TEC 植入 IVD 可保持椎间盘高度、终板和纤维环结构，并且在术后 6 周时与假手术组具有相似的生物力学特征。再生 IVD 的结构可维持至 6 个月。此外，ADSC-TEC 植入可减轻植入后 6 个月时与年龄相关的生物力学恶化的影响。这些结果表明，使用 ADSC-TEC 可以成为治疗 IVD 退变的有效方法。
我们开发了脂肪间充质干细胞衍生的无支架组织工程构建体（ADSC-TEC）作为一种新型细胞治疗系统。ADSC-TEC 植入大鼠全核切除的椎间盘空间可在组织学和生物力学上再生椎间盘（IVD）。ADSC-TEC 的再生能力是通过其对纤维环细胞的营养作用和对椎间空间的负载分担作用发挥的。有趣的是，与正常大鼠的 IVD 相比，ADSC-TEC 再生的 IVD 对年龄相关的恶化的敏感性较低。因此，将 ADSC-TEC 应用于退变的椎间盘可以作为治疗各种与 IVD 结构和功能衰竭相关疾病的替代疗法。
