Chen Chunxiu, Chen Fengfeng, Yao Chengye, Shu Shaofang, Feng Juan, Hu Xiaoling, Hai Quan, Yao Shanglong, Chen Xiangdong
Department of Anesthesiology, Institute of Anesthesiology and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Huaxi MR Research Center, Department of Radiology, West China Hospital, Sichuan University, Chengdu, China.
Neurochem Res. 2016 Dec;41(12):3250-3260. doi: 10.1007/s11064-016-2051-5. Epub 2016 Sep 21.
Neuropathic pain (NP) is a clinically incurable disease with miscellaneous causes, complicated mechanisms and available therapies show poor curative effect. Some recent studies have indicated that neuroinflammation plays a vital role in the occurrence and promotion of NP and anti-inflammatory therapy has the potential to relieve the pain. During the past decades, mesenchymal stem cells (MSCs) with properties of multipotentiality, low immunogenicity and anti-inflammatory activity have showed excellent therapeutic effects in cell therapy from animal models to clinical application, thus aroused great attention. However there are no reports about the effect of intrathecal human umbilical cord-derived mesenchymal stem cells (HUC-MSCs) on NP which is induced by peripheral nerve injury. Therefore, in this study, intrathecally transplanted HUC-MSCs were utilized to examine the effect on neuropathic pain induced by a rat model with spinal nerve ligation (SNL), so as to explore the possible mechanism of those effects. As shown in the results, the HUC-MSCs transplantation obviously ameliorated SNL-induced mechanical allodynia and thermal hyperalgesia, which was related to the inhibiting process of neuroinflammation, including the suppression of activated astrocytes and microglia, as well as the significant reduction of pro-inflammatory cytokines Interleukin-1β (IL-1β) and Interleukin -17A (IL-17A) and the up-regulation of anti-inflammatory cytokine Interleukin -10 (IL-10). Therefore, through the effect on glial cells, pro-inflammatory and anti-inflammatory cytokine, the targeting intrathecal HUC-MSCs may offer a novel treatment strategy for NP.
神经病理性疼痛(NP)是一种临床难以治愈的疾病,病因多样,机制复杂,现有治疗方法疗效不佳。最近的一些研究表明,神经炎症在NP的发生和发展中起重要作用,抗炎治疗有可能缓解疼痛。在过去几十年中,具有多能性、低免疫原性和抗炎活性的间充质干细胞(MSCs)在从动物模型到临床应用的细胞治疗中显示出优异的治疗效果,因此引起了极大关注。然而,关于鞘内注射人脐带间充质干细胞(HUC-MSCs)对周围神经损伤诱导的NP的影响尚无报道。因此,在本研究中,利用鞘内移植HUC-MSCs来研究其对脊髓神经结扎(SNL)大鼠模型诱导的神经病理性疼痛的影响,以探讨其可能的作用机制。结果表明,HUC-MSCs移植明显改善了SNL诱导的机械性异常性疼痛和热痛觉过敏,这与神经炎症的抑制过程有关,包括活化星形胶质细胞和小胶质细胞的抑制,以及促炎细胞因子白细胞介素-1β(IL-1β)和白细胞介素-17A(IL-17A)的显著降低和抗炎细胞因子白细胞介素-10(IL-10)的上调。因此,通过对神经胶质细胞、促炎和抗炎细胞因子的作用,靶向鞘内HUC-MSCs可能为NP提供一种新的治疗策略。