Takamura Hiroshi, Terashima Tomoya, Mori Kanji, Katagi Miwako, Okano Junko, Suzuki Yoshihisa, Imai Shinji, Kojima Hideto
Department of Stem Cell Biology and Regenerative Medicine, Shiga University of Medical Science, Shiga 520-2192, Japan.
Department of Orthopedic Surgery, Shiga University of Medical Science, Shiga, Japan.
Mol Ther Methods Clin Dev. 2020 Mar 30;17:657-665. doi: 10.1016/j.omtm.2020.03.020. eCollection 2020 Jun 12.
Treating neuropathic pain is a critical clinical issue. Although numerous therapies have been proposed, effective treatments have not been established. Therefore, safe and feasible treatment methods are urgently needed. In this study, we investigated the therapeutic effects of autologous intrathecal administration of bone-marrow-derived mononuclear cells (MNCs) on neuropathic pain. We generated a mouse model of neuropathic pain by transecting the spinal nerve and evaluated neuropathic pain by measuring the mechanical threshold in the following 14 days. Mice in the MNC injection group had a higher mechanical threshold than those in the buffer group. We assessed the effect of MNC treatment on the dorsal root ganglia and spinal cord by immunohistochemistry, mRNA expression, and cytokine assay. The migration and accumulation of microglia were significantly suppressed in the MNC group, and the mRNA expression of inflammatory cytokines such as interleukin (IL)-6, IL-1β, and tumor necrosis factor alpha (TNF-α) was markedly downregulated. Furthermore, MNC administration tended to suppress various cytokines in the cerebrospinal fluid of the model mice. In conclusion, our results suggest that intrathecal injection of MNCs relieves neuropathic pain and might be a promising cell therapy for the treatment of this condition.
治疗神经性疼痛是一个关键的临床问题。尽管已经提出了许多治疗方法，但尚未确立有效的治疗方案。因此，迫切需要安全可行的治疗方法。在本研究中，我们调查了自体鞘内注射骨髓来源的单核细胞（MNCs）对神经性疼痛的治疗效果。我们通过切断脊神经建立了神经性疼痛小鼠模型，并在接下来的14天内通过测量机械阈值来评估神经性疼痛。MNC注射组小鼠的机械阈值高于缓冲液组。我们通过免疫组织化学、mRNA表达和细胞因子检测评估了MNC治疗对背根神经节和脊髓的影响。MNC组小胶质细胞的迁移和聚集受到显著抑制，白细胞介素（IL）-6、IL-1β和肿瘤坏死因子α（TNF-α）等炎性细胞因子的mRNA表达明显下调。此外，注射MNCs有抑制模型小鼠脑脊液中各种细胞因子的趋势。总之，我们的结果表明，鞘内注射MNCs可缓解神经性疼痛，可能是治疗这种疾病的一种有前景的细胞疗法。
