A novel strategy for spinal cord reconstruction via vascularized allogeneic spinal cord transplantation combine spinal cord fusion

IF 4.8 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics Pub Date : 2024-09-23 DOI:10.1111/cns.70020

Weihua Zhang, Rongyu Lan, Tingting Shen, Jie Qin, Zhihui Wang, Jiayang Chen, Jiaxing Wang, Zhuotan Wu, Yudong Xu, Yangyang Shen, Qikai Lin, Yuan Chen, Yi Wei, Yiwen Liu, Yuance Ning, Yiyan Zhou, Liji Deng, Linxuan Han, Xiaofei Wu, Haixuan Deng, Zhenbin Cao, Xianping Yao, Xiaoping Ren

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Abstract

Aims

Spinal cord injuries (SCI) pose persistent challenges in clinical practice due to the secondary injury. Drawing from our experience in spinal cord fusion (SCF), we propose vascularized allogeneic spinal cord transplantation (vASCT) as a novel approach for SCI, much like organ transplantation has revolutionized organ failure treatment and vascularized composite-tissue allotransplantation has addressed limb defects.

Materials and Methods

In this study, 24 dogs were paired and underwent vASCT, with donor spinal cord grafts and polyethylene glycol (PEG) application for SCF. The experimental group (n = 8) received tacrolimus and methylprednisolone, while the control group (n = 4) received only methylprednisolone. Safety and efficacy of vASCT were evaluated through electrophysiology, imaging, and 6-month follow-up.

Results

The experimental group showed substantial recovery in hind limb motor function. Imaging revealed robust survival of spinal cord grafts and restoration of spinal cord continuity. In contrast, the control group maintained hind limb paralysis, with imaging confirming spinal cord graft necrosis and extensive defects. Electrophysiologically, the experimental group exhibited restored motor evoked potential signal conduction postoperatively, unlike the control group. Notably, PEG application during vASCT led to signal conduction recovery in intraoperative spinal cord evoked potential examinations for all dogs.

Conclusion

In the vASCT surgical model, the combination of PEG with tacrolimus has demonstrated the ability to reconstruct spinal cord continuity and restore hind limb motor function in beagles. Notably, a low dose of tacrolimus has also exhibited an excellent anti-immune rejection effect. These findings highlight vASCT's potential promise as a therapeutic strategy for addressing irreversible SCI.

Abstract Image

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通过血管化异体脊髓移植联合脊髓融合进行脊髓重建的新策略。

目的：脊髓损伤（SCI）会造成二次损伤，给临床实践带来持续挑战。借鉴脊髓融合术（SCF）的经验，我们提出血管化异体脊髓移植（vASCT）作为治疗SCI的新方法，就像器官移植彻底改变了器官衰竭的治疗，血管化复合组织异体移植解决了肢体缺损问题一样：在这项研究中，24 只狗配对接受了 vASCT，供体脊髓移植物和聚乙二醇（PEG）应用于 SCF。实验组（n = 8）接受他克莫司和甲基强的松龙治疗，对照组（n = 4）仅接受甲基强的松龙治疗。通过电生理学、影像学和 6 个月的随访评估了 vASCT 的安全性和有效性：结果：实验组后肢运动功能显著恢复。成像显示脊髓移植物存活率高，脊髓连续性得到恢复。相比之下，对照组后肢仍然瘫痪，影像学证实脊髓移植物坏死和广泛缺损。在电生理学上，实验组与对照组不同，术后运动诱发电位信号传导得到恢复。值得注意的是，在 vASCT 期间应用 PEG 可使所有犬的术中脊髓诱发电位检查信号传导恢复：结论：在 vASCT 手术模型中，PEG 与他克莫司的联合应用已证明能够重建小猎犬脊髓的连续性并恢复其后肢运动功能。值得注意的是，小剂量他克莫司也表现出了极佳的抗免疫排斥效果。这些研究结果突显了 vASCT 作为一种治疗策略在解决不可逆 SCI 方面的潜在前景。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

CNS Neuroscience & Therapeutics 医学-神经科学

CiteScore

7.30

自引率

12.70%

发文量

240

审稿时长

2 months

期刊介绍： CNS Neuroscience & Therapeutics provides a medium for rapid publication of original clinical, experimental, and translational research papers, timely reviews and reports of novel findings of therapeutic relevance to the central nervous system, as well as papers related to clinical pharmacology, drug development and novel methodologies for drug evaluation. The journal focuses on neurological and psychiatric diseases such as stroke, Parkinson’s disease, Alzheimer’s disease, depression, schizophrenia, epilepsy, and drug abuse.