Transplantation of Wnt4-modified neural stem cells mediate M2 polarization to improve inflammatory micro-environment of spinal cord injury.
Transplantation of Wnt4-modified neural stem cells mediate M2 polarization to improve inflammatory micro-environment of spinal cord injury.
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WNT4基因修饰的神经干细胞移植介导M2极化，改善脊髓损伤的炎性微环境。
DOI：
10.1111/cpr.13415
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发表时间：
2023-08
影响因子：
8.5
通讯作者：
中科院分区：
文献类型：
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作者：
神经干细胞（NSCs）移植被认为是脊髓损伤（SCI）后神经回路重新连接的一种潜在策略，但由于脊髓损伤的炎症微环境较差，其治疗效果仍不理想。既往研究认为神经保护和炎症免疫调节是NSCs移植最重要的机制。此外，Wnt4已被认为具有神经发生和抗炎作用，因此它将成为NSCs移植的重要辅助药物。我们的单细胞序列表明，巨噬细胞是脊髓损伤后炎症反应的最重要贡献者，巨噬细胞与星形胶质细胞的相互作用可能是脊髓损伤炎症微环境的最关键因素。我们进一步报道了利用NSCs -巨噬细胞共培养系统证实Wnt4修饰的NSCs与巨噬细胞之间相互作用的第一个证据。Wnt4修饰的NSCs通过抑制TLR4/NF - κB信号通路诱导巨噬细胞M2极化，抑制M1极化；M2细胞通过MAPK/JNK信号通路促进NSCs的神经元分化。在体内，移植Wnt4修饰的NSCs通过诱导巨噬细胞M2极化和抑制M1极化改善炎症微环境，促进轴突再生和组织修复。目前的研究表明，移植Wnt4修饰的NSCs可介导巨噬细胞的M2极化，促进脊髓损伤修复。我们的新发现将为脊髓损伤提供更多的见解，并有助于确定新的治疗策略。神经干细胞（NSCs）移植是治疗脊髓损伤（SCI）的一种有前景的策略。然而，脊髓损伤的炎症微环境较差，仍是其在临床上难以达到满意治疗效果的障碍。本研究发现，移植Wnt4修饰的NSCs可通过诱导脊髓损伤后巨噬细胞的M2极化和抑制M1极化，有效改善炎症微环境。Wnt4可能是神经干细胞移植治疗脊髓损伤的一个显著的潜在治疗靶点。
Neural stem cells (NSCs) transplantation has been considered as a potential strategy to reconnect the neural circuit after spinal cord injury (SCI) but the therapeutic effect was still unsatisfied because of the poor inflammatory micro‐environment of SCI. Previous study reported that neuroprotection and inflammatory immunomodulation were considered to be most important mechanism of NSCs transplantation. In addition, Wnt4 has been considered to be neurogenesis and anti‐inflammatory so that it would be an essential assistant agent for NSCs transplantation. Our single cells sequence indicates that macrophages are the most important contributor of inflammatory response after SCI and the interaction between macrophages and astrocytes may be the most crucial to inflammatory microenvironment of SCI. We further report the first piece of evidence to confirm the interaction between Wnt4‐modified NSCs and macrophages using NSCs‐macrophages co‐cultured system. Wnt4‐modified NSCs induce M2 polarization and inhibit M1 polarization of macrophages through suppression of TLR4/NF‐κB signal pathway; furthermore, M2 cells promote neuronal differentiation of NSCs through MAPK/JNK signal pathway. In vivo, transplantation of Wnt4‐modified NSCs improves inflammatory micro‐environment through induce M2 polarization and inhibits M1 polarization of macrophages to promote axonal regeneration and tissue repair. The current study indicated that transplantation of Wnt4‐modified NSCs mediates M2 polarization of macrophages to promote spinal cord injury repair. Our novel findings would provide more insight of SCI and help with identification of novel treatment strategy. Neural stem cells (NSCs) transplantation is a promising strategy to treat spinal cord injury (SCI). However, the poor inflammatory microenvironment of SCI is still the barrier for it to reach satisfied therapeutic effect in clinic. Here, we unveiled that transplantation of Wnt4‐modified NSCs effectively improves the inflammatory microenvironment through inducing M2 polarization and suppressing M1 polarization of macrophages after SCI. Wnt4 may be a remarkable potential therapeutic target in NSCs transplantation for SCI.
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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：
16.2
作者：
Gadani SP;Walsh JT;Lukens JR;Kipnis J
通讯作者：
Kipnis J
DOI：
10.1093/brain/awr339
发表时间：
2012-02
期刊：
Brain : a journal of neurology
影响因子：
--
作者：
Cusimano M;Biziato D;Brambilla E;Donegà M;Alfaro-Cervello C;Snider S;Salani G;Pucci F;Comi G;Garcia-Verdugo JM;De Palma M;Martino G;Pluchino S
通讯作者：
Pluchino S
影响因子：
5.3
作者：
Anwar MA;Al Shehabi TS;Eid AH
通讯作者：
Eid AH
DOI：
10.1523/jneurosci.3257-09.2009
发表时间：
2009-10-28
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Kigerl KA;Gensel JC;Ankeny DP;Alexander JK;Donnelly DJ;Popovich PG
通讯作者：
Popovich PG