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脊髓损伤后,体内对少突胶质前体细胞进行重编程可改善膀胱功能。

in vivo Reprogramming of NG2 Glia Improves Bladder Function After Spinal Cord Injury.

作者信息

Tai Wenjiao, Shang Junkui, Zhao Peiqi, Li Wei, Shen Tianjin, Zhong Xiaoling, Zou Yuhua, Chen Bo, Zhang Chun-Li

机构信息

Department of Molecular Biology, Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

Equal contribution.

出版信息

bioRxiv. 2025 Jul 31:2025.07.28.667292. doi: 10.1101/2025.07.28.667292.

DOI:10.1101/2025.07.28.667292
PMID:40766438
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12324377/
Abstract

Neurogenic bladder is a debilitating consequence of spinal cord injury (SCI), with few treatment options that restore voluntary voiding. Here, we show that SOX2-mediated in vivo reprogramming of NG2 glia improves bladder function in a clinically relevant mouse model of contusive SCI. NG2 glia reprogramming induces adult neurogenesis, reduces glial scarring, and significantly improves urinary performance, as measured by voiding assays and conscious cystometry. Functional recovery correlates positively with neurogenesis and negatively with glial scarring. These findings demonstrate that SOX2-mediated glial reprogramming promotes autonomic repair and offers a regenerative strategy for neurogenic bladder after SCI.

摘要

神经源性膀胱是脊髓损伤(SCI)的一种使人衰弱的后果,恢复自主排尿的治疗选择很少。在这里,我们表明,SOX2介导的体内NG2胶质细胞重编程可改善临床上相关的挫伤性SCI小鼠模型的膀胱功能。NG2胶质细胞重编程可诱导成体神经发生,减少胶质瘢痕形成,并通过排尿试验和清醒膀胱测压法测量,显著改善排尿性能。功能恢复与神经发生呈正相关,与胶质瘢痕形成呈负相关。这些发现表明,SOX2介导的胶质细胞重编程促进自主修复,并为SCI后神经源性膀胱提供了一种再生策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c30/12324377/aacafb97391c/nihpp-2025.07.28.667292v1-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c30/12324377/780ba4583fd2/nihpp-2025.07.28.667292v1-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c30/12324377/ea1aab0f1fc0/nihpp-2025.07.28.667292v1-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c30/12324377/c532a69c486e/nihpp-2025.07.28.667292v1-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c30/12324377/aacafb97391c/nihpp-2025.07.28.667292v1-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c30/12324377/780ba4583fd2/nihpp-2025.07.28.667292v1-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c30/12324377/ea1aab0f1fc0/nihpp-2025.07.28.667292v1-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c30/12324377/c532a69c486e/nihpp-2025.07.28.667292v1-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c30/12324377/aacafb97391c/nihpp-2025.07.28.667292v1-f0004.jpg

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本文引用的文献

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Nat Med. 2024 Dec;30(12):3676-3686. doi: 10.1038/s41591-024-03306-x. Epub 2024 Dec 2.
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Reduction of prolonged excitatory neuron swelling after spinal cord injury improves locomotor recovery in mice.脊髓损伤后减少兴奋性神经元肿胀可改善小鼠的运动功能恢复。
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Non-invasive spinal cord electrical stimulation for arm and hand function in chronic tetraplegia: a safety and efficacy trial.
非侵入性脊髓电刺激治疗慢性四肢瘫患者上肢和手功能:一项安全性和有效性试验。
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Recovery of walking after paralysis by regenerating characterized neurons to their natural target region.通过将特征化神经元再生到其自然靶区来恢复瘫痪后的行走功能。
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In vivo cell fate reprogramming for spinal cord repair.体内细胞命运重编程用于脊髓修复。
Curr Opin Genet Dev. 2023 Oct;82:102090. doi: 10.1016/j.gde.2023.102090. Epub 2023 Jul 26.
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Consequences of spinal cord injury on the sympathetic nervous system.脊髓损伤对交感神经系统的影响。
Front Cell Neurosci. 2023 Feb 28;17:999253. doi: 10.3389/fncel.2023.999253. eCollection 2023.
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The neurons that restore walking after paralysis.瘫痪后恢复行走的神经元。
Nature. 2022 Nov;611(7936):540-547. doi: 10.1038/s41586-022-05385-7. Epub 2022 Nov 9.
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Neurogenic Bladder Physiology, Pathogenesis, and Management after Spinal Cord Injury.脊髓损伤后神经源性膀胱的生理学、发病机制及管理
J Pers Med. 2022 Jun 14;12(6):968. doi: 10.3390/jpm12060968.
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