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

• Published in: CNS neuroscience & therapeutics 2024-09, Vol.30 (9), p.e70020-n/a
• Main Authors: Zhang, Weihua, Lan, Rongyu, Shen, Tingting, Qin, Jie, Wang, Zhihui, Chen, Jiayang, Wang, Jiaxing, Wu, Zhuotan, Xu, Yudong, Shen, Yangyang, Lin, Qikai, Chen, Yuan, Wei, Yi, Liu, Yiwen, Ning, Yuance, Zhou, Yiyan, Deng, Liji, Han, Linxuan, Wu, Xiaofei, Deng, Haixuan, Cao, Zhenbin, Yao, Xianping, Ren, Xiaoping
• Format: Article
• Language: English
• Subjects: Allografts; Animals; Clinical medicine; Clinical trials; Conduction; Dogs; Electrophysiology; Evoked Potentials, Motor - drug effects; Evoked Potentials, Motor - physiology; Female; Females; Graft rejection; Immunosuppressive Agents - pharmacology; Immunosuppressive Agents - therapeutic use; Injuries; Limbs; Male; Methylprednisolone; Methylprednisolone - therapeutic use; Motor evoked potentials; Motor task performance; Original; Paralysis; Pharmaceuticals; Polyethylene glycol; Reconstructive surgery; Recovery of function; Recovery of Function - drug effects; Recovery of Function - physiology; Spinal Cord; spinal cord defect; spinal cord fusion; Spinal cord injuries; Spinal Cord Injuries - surgery; Spinal Cord Injuries - therapy; spinal cord injury; Spinal Fusion - methods; Surgery; Tacrolimus; Tacrolimus - pharmacology; Tacrolimus - therapeutic use; Transplantation; Transplantation, Homologous - methods; Transplants & implants; vascularized allogeneic spinal cord transplantation; Veins & arteries
• ISSN: 1755-5930; 1755-5949; 1755-5949
• DOI: 10.1111/cns.70020

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. In this work, we proposed that vascularized allogeneic spinal cord transplantation (vASCT) might offer a new surgical approach for treating spinal cord injury. In the vASCT surgical model, the combination of polyethylene glycol with tacrolimus demonstrated the ability to reconstruct spinal cord continuity and restore hind limb motor function in beagles. The safety and efficacy of vASCT were verified by behavioral evaluation, electrophysiological examination and imaging examination.