Department of Neurosurgery, Beaumont Health System, Royal Oak, Michigan.
OUWB School of Medicine, Oakland University, Rochester, Michigan.
Neurosurgery. 2019 Jan 1;84(1):272-283. doi: 10.1093/neuros/nyy012.
Degenerative disc disease (DDD) is a common spinal disorder that manifests with neck and lower back pain caused by the degeneration of intervertebral discs (IVDs). Currently, there is no treatment to cure this debilitating ailment.
To investigate the potential of nucleus pulposus (NP)-like cells (NPCs) derived from human umbilical cord mesenchymal stem cells (MSCs) to restore degenerated IVDs using a rabbit DDD model.
NPCs differentiated from MSCs were characterized using quantitative real-time reverse transcription polymerase chain reaction and immunocytochemical analysis. MSCs and NPCs were labeled with fluorescent dye, PKH26, and transplanted into degenerated IVDs of a rabbit model of DDD (n = 9 each). Magnetic resonance imaging of the IVDs was performed before and after IVD degeneration, and following cell transplantation. IVDs were extracted 8 wk post-transplantation and analyzed by various biochemical, immunohistological, and molecular techniques.
NPC derivatives of MSCs expressed known NP-specific genes, SOX9, ACAN, COL2, FOXF1, and KRT19. Transplanted cells survived, dispersed, and integrated into the degenerated IVDs. IVDs augmented with NPCs showed significant improvement in the histology, cellularity, sulfated glycosaminoglycan and water contents of the NP. In addition, expression of human genes, SOX9, ACAN, COL2, FOXF1, KRT19, PAX6, CA12, and COMP, as well as proteins, SOX9, ACAN, COL2, and FOXF1, suggest NP biosynthesis due to transplantation of NPCs. Based on these results, a molecular mechanism for NP regeneration was proposed.
The findings of this study demonstrating feasibility and efficacy of NPCs to regenerate NP should spur interest for clinical studies to treat DDD using cell therapy.
退行性椎间盘疾病（DDD）是一种常见的脊柱疾病，表现为颈部和下背部疼痛，由椎间盘（IVD）退变引起。目前，尚无治愈这种使人虚弱的疾病的方法。
使用兔 DDD 模型，研究源自人脐带间充质干细胞（MSCs）的髓核样细胞（NPCs）修复退变的 IVD 的潜力。
通过实时定量逆转录聚合酶链反应和免疫细胞化学分析对 MSC 分化的 NPCs 进行特征描述。将 MSCs 和 NPCs 用荧光染料 PKH26 标记，并移植到 DDD 兔模型退变的 IVD 中（每组各 9 例）。在 IVD 退变前、后和细胞移植后对 IVD 进行磁共振成像。移植后 8 周提取 IVD ，并通过多种生化、免疫组织化学和分子技术进行分析。
MSC 的 NPC 衍生物表达已知的 NP 特异性基因 SOX9、ACAN、COL2、FOXF1 和 KRT19。移植的细胞存活、分散并整合到退变的 IVD 中。用 NPC 扩增的 IVD 在组织学、细胞密度、硫酸软骨素糖胺聚糖和 NP 含水量方面均有显著改善。此外，人基因 SOX9、ACAN、COL2、FOXF1、KRT19、PAX6、CA12 和 COMP 的表达以及 SOX9、ACAN、COL2 和 FOXF1 蛋白的表达提示由于 NPC 移植而产生 NP 生物合成。基于这些结果，提出了 NP 再生的分子机制。
本研究结果表明 NPC 具有再生 NP 的可行性和有效性，这应该会激发人们对使用细胞疗法治疗 DDD 的临床研究的兴趣。
