Therapeutic effects of peripherally administrated neural crest stem cells on pain and spinal cord changes after sciatic nerve transection.
Therapeutic effects of peripherally administrated neural crest stem cells on pain and spinal cord changes after sciatic nerve transection.
复制标题
DOI：
10.1186/s13287-021-02200-4
复制
发表时间：
2021-03-15
影响因子：
7.5
通讯作者：
Jia X
中科院分区：
文献类型：
--
作者：
Zhang Y;Xu X;Tong Y;Zhou X;Du J;Choi IY;Yue S;Lee G;Johnson BN;Jia X
严重的周围神经损伤会严重影响患者的生活质量并诱发神经性疼痛。神经嵴干细胞（NCSCs）在周围神经损伤后的细胞治疗中表现出几个有吸引力的特征。在这里，我们在坐骨神经横断（SNT）模型中研究NCSC治疗的疗效和脊髓的相关变化。用无细胞和载细胞神经支架修复大鼠复杂坐骨神经间隙损伤12周（支架组和NCSC组分别）。采用走秀步态分析评估运动功能恢复情况。机械戒断阈值和热戒断潜伏期用于评估神经性疼痛的发展。免疫荧光法检测神经胶质细胞的活化情况。western blot检测脊髓细胞外信号调节激酶（ERK）、NF-κB P65、脑源性神经营养因子（BDNF）、生长相关蛋白(GAP)-43、降钙素基因相关肽（CGRP）、炎症因子水平。t台步态分析显示，NCSC组动物站立指数和最大强度At（%）高于无细胞支架组（支架组）（p < 0.05）。NCSC组同侧后爪内侧足底面机械和热异常性疼痛明显减轻。舒尼替尼（SNT）诱导同侧L4-5背角和腹角相对于对侧的胶质纤维酸性蛋白（GFAP）（星形胶质细胞）和离子钙结合受体分子1 (Iba-1)（小胶质细胞）上调。免疫荧光分析显示星形胶质细胞和小胶质细胞活性降低。ERK和NF-κB信号的激活以及瞬时受体电位香草素1 （TRPV1）的表达下调。ncsc负载神经支架减轻snt诱导的神经性疼痛，改善坐骨神经修复后的运动功能恢复。NCSCs还可以保护脊髓免受snt诱导的胶质细胞激活和中枢致敏。在线版本包含补充材料，可在10.1186/s13287-021-02200-4获得。
Severe peripheral nerve injury significantly affects patients’ quality of life and induces neuropathic pain. Neural crest stem cells (NCSCs) exhibit several attractive characteristics for cell-based therapies following peripheral nerve injury. Here, we investigate the therapeutic effect of NCSC therapy and associated changes in the spinal cord in a sciatic nerve transection (SNT) model. Complex sciatic nerve gap injuries in rats were repaired with cell-free and cell-laden nerve scaffolds for 12 weeks (scaffold and NCSC groups, respectively). Catwalk gait analysis was used to assess the motor function recovery. The mechanical withdrawal threshold and thermal withdrawal latency were used to assess the development of neuropathic pain. Activation of glial cells was examined by immunofluorescence analyses. Spinal levels of extracellular signal-regulated kinase (ERK), NF-κB P65, brain-derived neurotrophic factor (BDNF), growth-associated protein (GAP)-43, calcitonin gene-related peptide (CGRP), and inflammation factors were calculated by western blot analysis. Catwalk gait analysis showed that animals in the NCSC group exhibited a higher stand index and Max intensity At (%) relative to those that received the cell-free scaffold (scaffold group) (p < 0.05). The mechanical and thermal allodynia in the medial-plantar surface of the ipsilateral hind paw were significantly relieved in the NCSC group. Sunitinib (SNT)-induced upregulation of glial fibrillary acidic protein (GFAP) (astrocyte) and ionized calcium-binding adaptor molecule 1 (Iba-1) (microglia) in the ipsilateral L4–5 dorsal and ventral horn relative to the contralateral side. Immunofluorescence analyses revealed decreased astrocyte and microglia activation. Activation of ERK and NF-κB signals and expression of transient receptor potential vanilloid 1 (TRPV1) expression were downregulated. NCSC-laden nerve scaffolds mitigated SNT-induced neuropathic pain and improved motor function recovery after sciatic nerve repair. NCSCs also protected the spinal cord from SNT-induced glial activation and central sensitization. The online version contains supplementary material available at 10.1186/s13287-021-02200-4.
登录
查看更多内容
影响因子：
3
作者：
Chen H;Du J;Zhang Y;Barnes K;Jia X
通讯作者：
Jia X
影响因子：
5.3
作者：
Duraku, Liron S.;Hossaini, Mehdi;Walbeehm, Erik T.
通讯作者：
Walbeehm, Erik T.
影响因子：
4.6
作者：
Hoeber, Jan;Trolle, Carl;Kozlova, Elena N.
通讯作者：
Kozlova, Elena N.
影响因子：
34.7
作者：
Brown, Guy C.;Neher, Jonas J.
通讯作者：
Neher, Jonas J.
影响因子：
5.3
作者：
Casals-Diaz, Laura;Vivo, Meritxell;Navarro, Xavier
通讯作者：
Navarro, Xavier