Nerve growth factor (NGF) with hypoxia response elements loaded by adeno-associated virus (AAV) combined with neural stem cells improve the spinal cord injury recovery.
Nerve growth factor (NGF) with hypoxia response elements loaded by adeno-associated virus (AAV) combined with neural stem cells improve the spinal cord injury recovery.
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腺相关病毒（AAV）负载缺氧反应元件的神经生长因子（NGF）联合神经干细胞改善脊髓损伤恢复
DOI：
10.1038/s41420-021-00701-y
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发表时间：
2021-10-21
影响因子：
7
通讯作者：
Zhu S
中科院分区：
文献类型：
--
作者：
Wu Q;Xiang Z;Ying Y;Huang Z;Tu Y;Chen M;Ye J;Dou H;Sheng S;Li X;Ying W;Zhu S
脊髓损伤后的缺血缺氧微环境使脊髓损伤的修复成为一个具有挑战性的问题。神经干细胞（neural stem cells，NSCs）在各种刺激下有很大的机会分化为神经元、星形胶质细胞、少突胶质细胞，被认为是脊髓损伤干细胞治疗的潜在来源。本研究利用腺相关病毒（adeno-associated virus，AAV）携带目的基因转染神经干细胞。转染的神经干细胞可表达由5个缺氧反应元件（5HRE）导航的神经生长因子（NGF）。因此，5HRE-NGF-NSCs可在缺氧部位特异性表达NGF，促进组织修复和功能恢复。基于脊髓损伤模型中神经细胞的再生和促进恢复的发现，通过运动评估、组织化学染色和分子检测，我们的结果表明5HRE-NGF-NSCs可以改善脊髓损伤大鼠的运动功能、神经元存活和分子表达。同时，自噬相关蛋白表达下调，表明5HRE-NGF-NSCs对自噬有抑制作用。我们的研究表明，5HRE-NGF-NSCs可能通过抑制自噬，提高神经细胞存活率，促进脊髓损伤的修复。新疗法还抑制了神经胶质瘢痕的增生并诱导轴突再生。5HRE-NGF-NSC的这些积极功能都表明了有希望的SCI治疗。
The ischemia and hypoxia microenvironment after spinal cord injury (SCI) makes SCI repair a challenging problem. With various stimulus, chances for neural stem cells (NSCs) to differentiate into neurons, astrocytes, oligodendrocytes are great and is considered as a potential source of the stem cell therapy to SCI. Our research used adeno-associated virus (AAV) to carry the target gene to transfect neural stem cells. Transfected NSCs can express nerve growth factor (NGF) navigated by five hypoxia-responsive elements (5HRE). Therefore, the 5HRE-NGF-NSCs could express NGF specifically in hypoxia sites to promote the tissue repair and function recovery. Based on the regeneration of neurocytes and promotion of the recovery found in SCI models, via locomotor assessment, histochemical staining and molecular examinations, our results demonstrated that 5HRE-NGF-NSCs could improve the motor function, neurons survival and molecules expression of SCI rats. Meanwhile, the downregulated expression of autophagy-related proteins indicated the inhibitive effect of 5HRE-NGF-NSCs on autophagy. Our research showed that 5HRE-NGF-NSCs contribute to SCI repair which might via inhibiting autophagy and improving the survival rate of neuronal cells. The new therapy also hampered the hyperplasia of neural glial scars and induced axon regeneration. These positive functions of 5HRE-NGF-NSCs all indicate a promising SCI treatment.
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影响因子：
6.1
作者：
Kanno, Haruo;Ozawa, Hiroshi;Itoi, Eiji
通讯作者：
Itoi, Eiji
影响因子：
3.8
作者：
Lee YK;Lee JA
通讯作者：
Lee JA
自噬诱导可稳定微管并促进脊髓损伤后轴突再生。
DOI：
10.1073/pnas.1611282113
发表时间：
2016-10-04
影响因子：
11.1
作者：
He, Miao;Ding, Yuetong;Luo, Zhen-Ge
通讯作者：
Luo, Zhen-Ge
影响因子：
2.2
作者：
Lee, B. B.;Cripps, R. A.;Wing, P. C.
通讯作者：
Wing, P. C.
DOI：
10.1016/j.bbi.2020.09.026
发表时间：
2021-01
期刊：
Brain, behavior, and immunity
影响因子：
--
作者：
Amo-Aparicio J;Sanchez-Fernandez A;Li S;Eisenmesser EZ;Garlanda C;Dinarello CA;Lopez-Vales R
通讯作者：
Lopez-Vales R