PDF(Pubmed)
Abstract：
UNASSIGNED: Neuropathic pain has been considered as one of the most serious chronic pain subtypes and causes intolerable suffering to patients physically and mentally. This study aimed to verify the analgesic effect of intravenous administration of human umbilical cord mesenchymal stem cells (HUC-MSCs) upon rats with chronic constriction injury (CCI)-induced neuropathic pain and the concomitant mechanism via modulating microglia.
UNASSIGNED: 30 male SD rats were randomized divided into three groups (n = 10 per group): Sham + Saline group (S&S group), CCI + Saline group (C&S group) and CCI + HUC-MSCs group (C&U group). Rats were injected with either saline or HUC-MSCs via the caudal vein on the 7th day after modelling. The paw mechanical withdrawal threshold (PMWT) and thermal withdrawal latency (TWL) of the ligation side were measured before (day 0) and after (day 1, 3, 5, 7, 9, 11, 13, and 15) modelling. On day 15 after modelling, western-blotting and immunofluorescent staining were used to assess the expressive abundance of Iba-1 (a typical biomarker of activated microglia) in the ligation side of the spinal cord dorsal horn, and ultrastructural changes of the ligation of sciatic nerve were evaluated by transmission electron microscope (TEM).
UNASSIGNED: Compared with the S&S group, PMWT and TWL in the C&S group were significantly decreased on day 5 and then persisted to day 15 after modelling (C&S vs S&S, P < 0.05), while a significant amelioration of mechanical hyperalgesia (day 13, day 15) and thermal allodynia (day 9, day 11, day 15) was observed in the C&U group (C&U vs C&S, P < 0.05). Meanwhile, the expression of Iba-1 was significantly suppressed by systemic infusion of HUC-MSCs in the C&U group according to western-blotting and immunofluorescent staining analyses (P < 0.05). With the aid of TEM detection, we intuitively noticed the efficacious reconstruction of the laminate structure of the sciatic nerve ligation, elimination of mitochondrial swelling, and formation of new myelination were noted on day 15 after modelling in the C&U group.
UNASSIGNED: Overall, intravenous administration of HUC-MSCs systemically revealed an ameliorative effect upon CCI-induced neuropathic pain in SD rats by inhibiting microglia activation in the dorsal horn of the impaired spinal cord and alleviating sciatic nerve injury. Our findings supply new references for the further development of HUC-MSCs-based cytotherapy for neuropathic pain administration.
UNASSIGNED: 30 male SD rats were randomized divided into three groups (n = 10 per group): Sham + Saline group (S&S group), CCI + Saline group (C&S group) and CCI + HUC-MSCs group (C&U group). Rats were injected with either saline or HUC-MSCs via the caudal vein on the 7th day after modelling. The paw mechanical withdrawal threshold (PMWT) and thermal withdrawal latency (TWL) of the ligation side were measured before (day 0) and after (day 1, 3, 5, 7, 9, 11, 13, and 15) modelling. On day 15 after modelling, western-blotting and immunofluorescent staining were used to assess the expressive abundance of Iba-1 (a typical biomarker of activated microglia) in the ligation side of the spinal cord dorsal horn, and ultrastructural changes of the ligation of sciatic nerve were evaluated by transmission electron microscope (TEM).
UNASSIGNED: Compared with the S&S group, PMWT and TWL in the C&S group were significantly decreased on day 5 and then persisted to day 15 after modelling (C&S vs S&S, P < 0.05), while a significant amelioration of mechanical hyperalgesia (day 13, day 15) and thermal allodynia (day 9, day 11, day 15) was observed in the C&U group (C&U vs C&S, P < 0.05). Meanwhile, the expression of Iba-1 was significantly suppressed by systemic infusion of HUC-MSCs in the C&U group according to western-blotting and immunofluorescent staining analyses (P < 0.05). With the aid of TEM detection, we intuitively noticed the efficacious reconstruction of the laminate structure of the sciatic nerve ligation, elimination of mitochondrial swelling, and formation of new myelination were noted on day 15 after modelling in the C&U group.
UNASSIGNED: Overall, intravenous administration of HUC-MSCs systemically revealed an ameliorative effect upon CCI-induced neuropathic pain in SD rats by inhibiting microglia activation in the dorsal horn of the impaired spinal cord and alleviating sciatic nerve injury. Our findings supply new references for the further development of HUC-MSCs-based cytotherapy for neuropathic pain administration.
摘要：
■神经性疼痛已被认为是最严重的慢性疼痛亚型之一,并对患者的身体和精神造成无法忍受的痛苦。本研究旨在验证人脐带间充质干细胞(HUC-MSCs)对慢性缩窄性损伤(CCI)诱导的神经病理性疼痛大鼠的镇痛作用及其通过调节小胶质细胞的作用机制。
■30只雄性SD大鼠随机分为三组(每组10只):假盐水组(S&S组),CCI+盐水组(C&S组)和CCI+HUC-MSCs组(C&U组)。在建模后的第7天，通过尾静脉注射盐水或HUC-MSC。在建模之前（第0天）和之后（第1、3、5、7、9、11、13和15天）测量结扎侧的爪机械缩回阈值（PMWT）和热缩回潜伏期（TWL）。建模后的第15天，免疫印迹和免疫荧光染色用于评估Iba-1（活化小胶质细胞的典型生物标志物）在脊髓背角结扎侧的表达丰度，透射电镜观察坐骨神经结扎的超微结构变化。
■与S&S组相比，C&S组的PMWT和TWL在第5天显著下降，然后持续到建模后第15天(C&SvsS&S，P<0.05),而在C&U组中观察到机械性痛觉过敏(第13天、第15天)和热异常性疼痛(第9天、第11天、第15天)的显著改善(C&UvsC&S,P<0.05)。同时,根据蛋白质印迹和免疫荧光染色分析，C＆U组系统输注HUC-MSCs可显著抑制Iba-1的表达（P<0.05）。借助TEM检测，我们直观地注意到坐骨神经结扎的层状结构的有效重建，消除线粒体肿胀，在C&U组建模后第15天发现新的髓鞘形成。
■总的来说，静脉内给予HUC-MSCs通过抑制受损脊髓背角的小胶质细胞活化和减轻坐骨神经损伤，对CCI诱导的SD大鼠神经病理性疼痛有系统的改善作用。我们的发现为进一步开发基于HUC-MSCs的用于神经性疼痛的细胞疗法提供了新的参考。
■30只雄性SD大鼠随机分为三组(每组10只):假盐水组(S&S组),CCI+盐水组(C&S组)和CCI+HUC-MSCs组(C&U组)。在建模后的第7天，通过尾静脉注射盐水或HUC-MSC。在建模之前（第0天）和之后（第1、3、5、7、9、11、13和15天）测量结扎侧的爪机械缩回阈值（PMWT）和热缩回潜伏期（TWL）。建模后的第15天，免疫印迹和免疫荧光染色用于评估Iba-1（活化小胶质细胞的典型生物标志物）在脊髓背角结扎侧的表达丰度，透射电镜观察坐骨神经结扎的超微结构变化。
■与S&S组相比，C&S组的PMWT和TWL在第5天显著下降，然后持续到建模后第15天(C&SvsS&S，P<0.05),而在C&U组中观察到机械性痛觉过敏(第13天、第15天)和热异常性疼痛(第9天、第11天、第15天)的显著改善(C&UvsC&S,P<0.05)。同时,根据蛋白质印迹和免疫荧光染色分析，C＆U组系统输注HUC-MSCs可显著抑制Iba-1的表达（P<0.05）。借助TEM检测，我们直观地注意到坐骨神经结扎的层状结构的有效重建，消除线粒体肿胀，在C&U组建模后第15天发现新的髓鞘形成。
■总的来说，静脉内给予HUC-MSCs通过抑制受损脊髓背角的小胶质细胞活化和减轻坐骨神经损伤，对CCI诱导的SD大鼠神经病理性疼痛有系统的改善作用。我们的发现为进一步开发基于HUC-MSCs的用于神经性疼痛的细胞疗法提供了新的参考。
