Department of Spinal Surgery, Daping Hospital, Research Institute of Surgery, Third Military Medical University (Army Medical University), Chongqing 400042, P.R. China.
Department of Spinal Surgery, Daping Hospital, Research Institute of Surgery, Third Military Medical University (Army Medical University), Chongqing 400042, P.R. China.
Mol Med Rep. 2020 Dec;22(6):4725-4733. doi: 10.3892/mmr.2020.11565. Epub 2020 Oct 6.
Spinal cord injury (SCI) is a devastating disorder that often results in temporary and/or permanent functional impairment below the injured level. To date, few satisfactory therapeutic strategies are available to treat SCI. Hence, exploring novel strategies for SCI is an essential public health concern. Cell transplantation therapy, which is associated with neuroprotection, immunomodulation, axon regeneration, neuronal relay formation and myelin regeneration, provides a promising therapeutic strategy for SCI. The neuronal stem cell (NSC) preconditioning method is an emerging approach, which facilitates NSC survival and neuronal differentiation after implantation. The aim of the present study was to develop a feasible candidate for cell‑based therapy following SCI in rats and to investigate the role of high mobility group box‑1 (HMGB1) in NSC activation. The results of the present study showed that transplantation of NSCs, preconditioned with 1 ng/ml HMGB1, facilitated functional improvement of injured spinal cords, as indicated by Basso, Beattie and Bresnahan mean scores, mechanical hypersensitivity and cold stimulation. Meanwhile, the histological examination of hematoxylin and eosin staining indicated that engraftment of HMGB1‑preconditioned NSCs resulted in decreased atrophy of the injured spinal cord. Meanwhile, the transplantation of HMGB1‑preconditioned NSCs resulted in an increased number of functional Nissl bodies in neurons, as detected by Nissl staining, and an increase in the number of βIII‑tubulin+ cells in the epicenter of injured spinal cords in rats with SCI. In addition, the results also demonstrated that 1 ng/ml HMGB1 promoted the differentiation of NSCs into neurons, and that the ERK signaling pathway played an important role in this process. In conclusion, the present data indicated that the preconditioning strategy with 1 ng/ml HMGB1 may present a feasible candidate for cell‑based therapy following SCI in rats, which may enlarge the scope of HMGB1 in NSC activation.
脊髓损伤 (SCI) 是一种破坏性疾病，常导致损伤水平以下的暂时和/或永久性功能障碍。迄今为止，很少有令人满意的治疗策略可用于治疗 SCI。因此，探索治疗 SCI 的新策略是一个重要的公共卫生关注点。细胞移植疗法与神经保护、免疫调节、轴突再生、神经元中继形成和髓鞘再生有关，为 SCI 提供了一种有前途的治疗策略。神经干细胞 (NSC) 预处理方法是一种新兴方法，可促进植入后 NSC 的存活和神经元分化。本研究旨在为大鼠 SCI 后的细胞治疗开发一种可行的候选物，并研究高迁移率族蛋白 B1 (HMGB1) 在 NSC 激活中的作用。本研究结果表明，移植经 1ng/ml HMGB1 预处理的 NSCs 可改善损伤脊髓的功能，Basso、Beattie 和 Bresnahan 平均评分、机械性超敏反应和冷刺激均表明这一点。同时，苏木精-伊红染色的组织学检查表明，HMGB1 预处理 NSCs 的移植导致损伤脊髓萎缩减少。同时，HMGB1 预处理 NSCs 的移植导致 Nissl 染色检测到神经元中功能性尼氏体数量增加，以及 SCI 大鼠损伤脊髓中心区 βIII-微管蛋白+细胞数量增加。此外，结果还表明，1ng/ml HMGB1 促进 NSCs 向神经元分化，ERK 信号通路在此过程中发挥重要作用。综上所述，本研究数据表明，1ng/ml HMGB1 的预处理策略可能为大鼠 SCI 后的细胞治疗提供一种可行的候选物，这可能扩大 HMGB1 在 NSC 激活中的作用范围。
