Department of Orthopedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, N15W7, Sapporo 060-8638, Japan.
PuREC/Bio-Venture, Shimane University, Izumo 693-8501, Japan.
Cells. 2023 Feb 3;12(3):505. doi: 10.3390/cells12030505.
Intervertebral disc (IVD) degeneration is a major cause of low back pain. However, treatments directly approaching the etiology of IVD degeneration and discogenic pain are not yet established. We previously demonstrated that intradiscal implantation of cell-free bioresorbable ultra-purified alginate (UPAL) gel promotes tissue repair and reduces discogenic pain, and a combination of ultra-purified, Good Manufacturing Practice (GMP)-compliant, human bone marrow mesenchymal stem cells (rapidly expanding clones; RECs), and the UPAL gel increasingly enhanced IVD regeneration in animal models. This study investigated the therapeutic efficacy of injecting a mixture of REC and UPAL non-gelling solution for discogenic pain and IVD regeneration in a rat caudal nucleus pulposus punch model. REC and UPAL mixture and UPAL alone suppressed not only the expression of TNF-α, IL-6, and TrkA ( < 0.01, respectively), but also IVD degeneration and nociceptive behavior compared to punching alone ( < 0.01, respectively). Furthermore, REC and UPAL mixture suppressed these expression levels and nociceptive behavior compared to UPAL alone ( < 0.01, respectively). These results suggest that this minimally invasive treatment strategy with a single injection may be applied to treat discogenic pain and as a regenerative therapy.
椎间盘(IVD)退变是导致腰痛的主要原因。然而,直接针对 IVD 退变和椎间盘源性疼痛病因的治疗方法尚未确立。我们之前的研究表明,椎间盘内植入无细胞的生物可吸收超纯藻酸盐(UPAL)凝胶可促进组织修复并减轻椎间盘源性疼痛,而超纯、符合良好生产规范(GMP)的人骨髓间充质干细胞(快速扩增克隆;RECs)与 UPAL 凝胶的组合在动物模型中可增强 IVD 再生。本研究在大鼠尾核髓核穿孔模型中,研究了注射 REC 和 UPAL 非凝胶溶液混合物治疗椎间盘源性疼痛和 IVD 再生的疗效。RECs 和 UPAL 混合物以及 UPAL 单独治疗均能抑制 TNF-α、IL-6 和 TrkA 的表达(分别为 < 0.01),同时与单独穿孔相比,还能抑制 IVD 退变和痛觉行为(分别为 < 0.01)。此外,RECs 和 UPAL 混合物与 UPAL 单独治疗相比,能抑制这些表达水平和痛觉行为(分别为 < 0.01)。这些结果表明,这种单次注射的微创治疗策略可能适用于治疗椎间盘源性疼痛和作为一种再生疗法。