AAV2-mediated and hypoxia response element-directed expression of bFGF in neural stem cells showed therapeutic effects on spinal cord injury in rats.
AAV2-mediated and hypoxia response element-directed expression of bFGF in neural stem cells showed therapeutic effects on spinal cord injury in rats.
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AAV2介导和缺氧反应元件在神经干细胞中定向表达bFGF对大鼠脊髓损伤有治疗作用
DOI：
10.1038/s41419-021-03546-6
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发表时间：
2021-03-15
影响因子：
9
通讯作者：
Xu J
中科院分区：
文献类型：
--
作者：
Zhu S;Ying Y;Ye J;Chen M;Wu Q;Dou H;Ni W;Xu H;Xu J
神经干细胞移植是脊髓损伤修复的研究热点之一。成纤维细胞生长因子（FGF）被认为是一种有前途的治疗脊髓损伤后神经损伤的药物。然而，由于SCI中的恶劣缺氧条件，在实施这些策略以修复SCI方面仍然存在挑战性问题。本研究利用腺相关病毒2型（AAV 2），构建了缺氧反应元件（HRE）调控的碱性成纤维细胞生长因子（bFGF）基因，并将其导入神经干细胞，获得了AAV 2 - 5 HRE-bFGF-NSCs。我们的研究结果表明，其治疗产生了短暂增加的bFGF在SCI中的表达，并且基于斜面测试、Basso-Beattie-Bresnahan（BBB）量表和足迹分析的分析，与载体对照（AAV 2 - 5 HRE-NSC）相比，改善了SCI后的功能恢复评分。机制研究表明，与对照组相比，AAV 2 - 5 HRE-bFGF-NSCs处理增加了神经元特异性神经元核蛋白（NeuN）、神经调节素GAP 43和神经丝蛋白NF 200的表达，而降低了胶质细胞酸性蛋白（GFAP）的表达。AAV 2 - 5 HRE-bFGF-NSCs处理组自噬相关蛋白LC 3-II和Beclin 1表达降低，P62蛋白表达增加。总之，我们的数据表明，AAV 2 - 5 HRE-bFGF-NSC治疗改善了SCI大鼠的恢复，这伴随着神经再生的证据，以及SCI诱导的胶质瘢痕形成和细胞自噬的抑制。因此，这项研究代表了AAV 2 - 5 HRE-bFGF-NSC在未来SCI修复临床试验中的潜在用途的一步。
Neural stem cell (NSCs) transplantation has been one of the hot topics in the repair of spinal cord injury (SCI). Fibroblast growth factor (FGF) is considered a promising nerve injury therapy after SCI. However, owing to a hostile hypoxia condition in SCI, there remains a challenging issue in implementing these tactics to repair SCI. In this report, we used adeno-associated virus 2 (AAV2), a prototype AAV used in clinical trials for human neuron disorders, basic FGF (bFGF) gene under the regulation of hypoxia response element (HRE) was constructed and transduced into NSCs to yield AAV2-5HRE-bFGF-NSCs. Our results showed that its treatment yielded temporally increased expression of bFGF in SCI, and improved scores of functional recovery after SCI compared to vehicle control (AAV2-5HRE-NSCs) based on the analyses of the inclined plane test, Basso–Beattie–Bresnahan (BBB) scale and footprint analysis. Mechanistic studies showed that AAV2-5HRE-bFGF-NSCs treatment increased the expression of neuron-specific neuronal nuclei protein (NeuN), neuromodulin GAP43, and neurofilament protein NF200 while decreased the expression of glial fibrillary acidic protein (GFAP) as compared to the control group. Further, the expressions of autophagy-associated proteins LC3-II and Beclin 1 were decreased, whereas the expression of P62 protein was increased in AAV2-5HRE-bFGF-NSCs treatment group. Taken together, our data indicate that AAV2-5HRE-bFGF-NSCs treatment improved the recovery of SCI rats, which is accompanied by evidence of nerve regeneration, and inhibition of SCI-induced glial scar formation and cell autophagy. Thus, this study represents a step forward towards the potential use of AAV2-5HRE-bFGF-NSCs for future clinical trials of SCI repair.
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影响因子：
3
作者：
Fujimaki, Hisako;Inoue, Gen;Takaso, Masashi
通讯作者：
Takaso, Masashi
影响因子：
2.2
作者：
Hou, H.;Zhang, L.;Tang, P.
通讯作者：
Tang, P.
缺氧调节腺病毒载体介导的 bFGF 表达可保护血清剥夺诱导的 PC12 细胞死亡
DOI：
10.1016/j.bbrc.2009.09.077
发表时间：
2009-12-04
影响因子：
3.1
作者：
Hu, Hou-Wen;Li, Xiao-Kun;Hou, Sheng T.
通讯作者：
Hou, Sheng T.
影响因子：
3.3
作者：
Fan B;Wei Z;Yao X;Shi G;Cheng X;Zhou X;Zhou H;Ning G;Kong X;Feng S
通讯作者：
Feng S
影响因子：
3
作者：
Falavigna，Asdrubal;Figueiro，Manuela Peletti;Radaelli，Lucas
通讯作者：
Radaelli，Lucas