Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Medical College of Zhejiang University, China; Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province, China.
Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Medical College of Zhejiang University, China; Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province, China.
Mater Sci Eng C Mater Biol Appl. 2019 Jun;99:1213-1225. doi: 10.1016/j.msec.2019.02.045. Epub 2019 Feb 16.
Intervertebral disc (IVD) degeneration is associated with lower back pain, with the dysfunction of nucleus pulposus (NP) cells instigating degeneration onset. Here, we developed an optimized decellularised NP scaffold that could induce mesenchymal stem cells (MSCs) into NP-like cells in vitro and rescue the degenerated IVD in vivo. We optimized a decellularisation protocol for porcine NP and evaluated the biological properties and microstructure of the NP scaffold. Through co-culture with MSCs, we analysed scaffold bioactivity and potential signalling pathways. We tested the therapeutic efficacy of the scaffold using an IVD degeneration model in vivo. The decellularisation protocol generally removed the cellular components of the NP and preserved the majority of the biological components and regular microstructure. MSCs seeded in the NP-ECM scaffold differentiated into NP-like cells in vitro; this change was attributed to activation of the TGF-β signalling pathway. The NP-ECM exhibited good cytocompatibility ex vivo and decelerated the degeneration of the IVD in vivo. These results indicate the successful establishment of a naturally-derived ECM material that could induce MSCs into NP cells and serve as a potential treatment for degenerated IVDs.
椎间盘（IVD）退变与下腰痛有关，其中，髓核（NP）细胞功能障碍引发退变发生。本研究开发了一种优化的去细胞 NP 支架，能够在体外将间充质干细胞（MSCs）诱导为 NP 样细胞，并在体内挽救退变的 IVD。我们优化了猪 NP 的去细胞化方案，并评估了 NP 支架的生物学特性和微观结构。通过与 MSCs 共培养，分析了支架的生物活性和潜在信号通路。我们通过体内 IVD 退变模型测试了支架的治疗效果。该去细胞化方案通常可以去除 NP 的细胞成分，并保留大多数生物成分和规则的微观结构。MSCs 在 NP-ECM 支架中培养可以体外分化为 NP 样细胞；这种变化归因于 TGF-β 信号通路的激活。NP-ECM 在体外具有良好的细胞相容性，并在体内减缓了 IVD 的退变。这些结果表明成功建立了一种天然衍生的 ECM 材料，能够将 MSCs 诱导为 NP 细胞，有望成为退变 IVD 的治疗方法。
