Transplantation of Wnt5a-modified NSCs promotes tissue repair and locomotor functional recovery after spinal cord injury.
Transplantation of Wnt5a-modified NSCs promotes tissue repair and locomotor functional recovery after spinal cord injury.
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DOI：
10.1038/s12276-020-00536-0
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发表时间：
2020-12
影响因子：
12.8
通讯作者：
Wan Y
中科院分区：
文献类型：
--
作者：
Li X;Peng Z;Long L;Lu X;Zhu K;Tuo Y;Chen N;Zhao X;Wang L;Wan Y
由于中枢神经系统（CNS）损伤后的轴突再连接和神经元再生的失败，传统的脊髓损伤治疗策略不足以修复运动功能。神经干细胞（NSC）移植被认为是修复脊髓损伤后神经回路的一种潜在策略，并且通常是可行的。然而，最可怕的问题是NSCs的神经元分化率非常有限。因此，诱导NSCs的神经元分化，提高NSCs的分化率在脊髓修复中至关重要。我们的研究结果表明，Wnt5a和miRNA200b-3p都能促进NSC向神经元分化，Wnt5a通过MAPK/JNK信号上调miRNA200b-3p的表达，促进NSC向神经元分化。Wnt5a可以通过上调miRNA200b-3p表达，抑制RhoA/Rock信号通路的激活，从而降低RhoA的表达，有报道称其抑制神经元分化。RhoA的过表达使Wnt5a和miRNA200b-3p的神经发生能力丧失。在体内，miRNA200b-3p是wnt5a诱导的NSC向神经元分化的关键，通过抑制RhoA/Rock信号传导促进脊髓损伤后运动功能和组织学恢复。这些发现为脊髓损伤提供了更多的见解，并有助于确定新的治疗策略。将关键分子掺入神经干细胞可提高其正确分化的能力，促进脊髓损伤后的修复。脊髓损伤会对患者的生活产生衰弱的影响，但目前还没有完全恢复运动和感觉的治疗方法。基于神经干细胞（NSCs）的治疗显示出希望，但最初的研究表明，许多NSCs分化为星形胶质细胞，而不是神经元，这是一种不传导神经冲动的支持性细胞，导致治疗失败。中国广州中山大学的万勇和王乐及其同事证明，向NSCs中添加一种名为Wnt5a的蛋白质和一种特定的microRNA分子，可以显著增加向神经元的分化。Wnt5a抑制信号通路，否则会干扰NSC分化。大鼠模型实验表明，该疗法改善了大鼠损伤后的运动功能和组织修复。
Traditional therapeutic strategies for spinal cord injury (SCI) are insufficient to repair locomotor function because of the failure of axonal reconnection and neuronal regeneration in the injured central nervous system (CNS). Neural stem cell (NSC) transplantation has been considered a potential strategy and is generally feasible for repairing the neural circuit after SCI; however, the most formidable problem is that the neuronal differentiation rate of NSCs is quite limited. Therefore, it is essential to induce the neuronal differentiation of NSCs and improve the differentiation rate of NSCs in spinal cord repair. Our results demonstrate that both Wnt5a and miRNA200b-3p could promote NSC differentiation into neurons and that Wnt5a upregulated miRNA200b-3p expression through MAPK/JNK signaling to promote NSC differentiation into neurons. Wnt5a could reduce RhoA expression by upregulating miRNA200b-3p expression to inhibit activation of the RhoA/Rock signaling pathway, which has been reported to suppress neuronal differentiation. Overexpression of RhoA abolished the neurogenic capacity of Wnt5a and miRNA200b-3p. In vivo, miRNA200b-3p was critical for Wnt5a-induced NSC differentiation into neurons to promote motor functional and histological recovery after SCI by suppressing RhoA/Rock signaling. These findings provide more insight into SCI and help with the identification of novel treatment strategies. Incorporating key molecules into neural stem cells enhances their ability to differentiate correctly and promote repair following spinal cord injury. Spinal cord injuries can have a debilitating effect on patients’ lives, yet there are no therapies that fully restore movement and sensation. Therapies based on neural stem cells (NSCs) show promise, but initial studies show many NSCs differentiate into astrocytes, supportive cells that do not conduct nerve impulses, instead of neurons, leading to treatment failure. Yong Wan and Le Wang at Sun Yat-sen University in Guangzhou, China, and co-workers demonstrated that adding a protein called Wnt5a and a specific microRNA molecule to NSCs significantly increases differentiation into neurons. Wnt5a suppresses a signalling pathway that otherwise interferes with NSC differentiation. Experiments on rat models showed that the therapy improved locomotor function and tissue repair after injury.
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影响因子：
4.6
作者：
Bresson, Laura;Faraldo, Marisa M.;Deugnier, Marie-Ange
通讯作者：
Deugnier, Marie-Ange
移植神经干细胞中富含亮氨酸重复序列和含有免疫球蛋白结构域的蛋白 1 的靶向抑制可促进脊髓损伤大鼠的神经元分化和功能恢复。
影响因子：
8.8
作者：
Chen, Ningning;Cen, Jing-sheng;Wan, Yong
通讯作者：
Wan, Yong
影响因子：
6.1
作者：
Gomes, Eduardo D;Silva, Nuno A;Salgado, Antonio J
通讯作者：
Salgado, Antonio J
影响因子：
4.6
作者：
Lanoue V;Langford M;White A;Sempert K;Fogg L;Cooper HM
通讯作者：
Cooper HM
影响因子：
2.2
作者：
Lee, B. B.;Cripps, R. A.;Wing, P. C.
通讯作者：
Wing, P. C.