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Autologous fibroblasts induce fibrosis of the nucleus pulposus to maintain the stability of degenerative intervertebral discs.
Bone Research ( IF 12.7 ) Pub Date : 2020-02-13 , DOI: 10.1038/s41413-019-0082-7
Chen Chen 1 , Tangjun Zhou 1 , Xiaojiang Sun 1 , Chen Han 1 , Kai Zhang 1 , Changqing Zhao 1 , Xunlin Li 1 , Haijun Tian 1 , Xiao Yang 1 , Yifan Zhou 1 , Zhiqian Chen 1 , An Qin 1 , Jie Zhao 1
Affiliation  

Lumbar degenerative disc diseases cause low back pain (LBP). The maintenance of the height and stability of the intervertebral disc (IVD) space is an effective treatment for LBP. The following study evaluated the effects of fibroblast injection on intervertebral disc degeneration (IDD) in a preclinical setting. Compared with the IDD group, the fibroblast treatment group demonstrated effective maintenance of IVD height, reduced endplate degeneration, and improved nuclear magnetic resonance signals and overall histological structure. In doing so, fibrotic IVDs maintained the stability and biomechanics of the vertebra. This finding is in agreement with clinical findings that human nucleus pulposus (NP) fibrosis is essential for the maintenance of IVD height and mechanical properties in patients following percutaneous endoscopic lumbar discectomy (PELD). Mechanistically, we demonstrated that injected fibroblasts not only proliferated but also induced NP cells to adopt a fibrotic phenotype via the secretion of TGF-β. Finally, to better mimic human conditions, the efficacy of autologous fibroblast injection in the treatment of IDD was further examined in a nonhuman primate cynomolgus monkey model due to their capacity for upright posture. We showed that the injection of fibroblasts could maintain the IVD height and rescue IVD signals in cynomolgus monkeys. Taken together, the results of our study reveal that autologous fibroblast injection can enhance the natural process of fibrosis during acute and subacute stages of stress-induced IDD. Fibrotic IVDs can maintain the stability, biological activity, and mechanical properties of the intervertebral space, thus providing a new direction for the treatment of intervertebral space-derived lumbar degenerative diseases.

中文翻译:

自体成纤维细胞诱导髓核纤维化,以维持变性椎间盘的稳定性。

腰椎间盘退变疾病引起下腰痛(LBP)。维持椎间盘(IVD)空间的高度和稳定性是治疗LBP的有效方法。以下研究在临床前环境中评估了成纤维细胞注射对椎间盘退变(IDD)的影响。与IDD组相比,成纤维细胞治疗组表现出有效维持IVD高度,减少终板变性,改善核磁共振信号和整体组织学结构。这样做,纤维化IVD保持了椎骨的稳定性和生物力学。该发现与临床发现一致,即在经皮内镜下腰椎间盘摘除术(PELD)后,人髓核(NP)纤维化对于维持IVD高度和机械性能至关重要。从机制上讲,我们证明注射的成纤维细胞不仅可以增殖,而且可以通过分泌TGF-β诱导NP细胞采用纤维化表型。最后,为了更好地模仿人类状况,由于其直立姿势的能力,在非人类灵长类食蟹猴模型中进一步检查了自体成纤维细胞注射治疗IDD的功效。我们表明,成纤维细胞的注射可以保持食蟹猴的IVD高度并挽救IVD信号。在一起 我们的研究结果表明,自体成纤维细胞注射可以在应激诱导的IDD的急性和亚急性阶段增强纤维化的自然过程。纤维化IVD可以维持椎间隙的稳定性,生物学活性和力学性能,从而为椎间隙衍生的腰椎退行性疾病的治疗提供新的方向。
更新日期:2020-02-13
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