Chen Szu-Han, Wu Chia-Ching, Tseng Wan-Ling, Lu Fu-I, Liu Ya-Hsin, Lin Shau-Ping, Lin Sheng-Che, Hsueh Yuan-Yu
Division of Plastic and Reconstructive Surgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Center of Cell Therapy, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Front Neurosci. 2023 Jun 29;17:1172740. doi: 10.3389/fnins.2023.1172740. eCollection 2023.
Compressive neuropathy, a common chronic traumatic injury of peripheral nerves, leads to variable impairment in sensory and motor function. Clinical symptoms persist in a significant portion of patients despite decompression, with muscle atrophy and persistent neuropathic pain affecting 10%-25% of cases. Excessive inflammation and immune cell infiltration in the injured nerve hinder axon regeneration and functional recovery. Although adipose-derived stem cells (ASCs) have demonstrated neural regeneration and immunomodulatory potential, their specific effects on compressive neuropathy are still unclear.
We conducted modified CCI models on adult male Sprague-Dawley rats to induce irreversible neuropathic pain and muscle atrophy in the sciatic nerve. Intraneural ASC injection and nerve decompression were performed. Behavioral analysis, muscle examination, electrophysiological evaluation, and immunofluorescent examination of the injured nerve and associated DRG were conducted to explore axon regeneration, neuroinflammation, and the modulation of inflammatory gene expression. Transplanted ASCs were tracked to investigate potential beneficial mechanisms on the local nerve and DRG.
Persistent neuropathic pain was induced by chronic constriction of the rat sciatic nerve. Local ASC treatment has demonstrated robust beneficial outcomes, including the alleviation of mechanical allodynia, improvement of gait, regeneration of muscle fibers, and electrophysiological recovery. In addition, locally transplanted ASCs facilitated axon remyelination, alleviated neuroinflammation, and reduced inflammatory cell infiltration of the injured nerve and associated dorsal root ganglion (DRG). Trafficking of the transplanted ASC preserved viability and phenotype less than 7 days but contributed to robust immunomodulatory regulation of inflammatory gene expression in both the injured nerve and DRG.
Locally transplanted ASC on compressed nerve improve sensory and motor recoveries from irreversible chronic constriction injury of rat sciatic nerve via alleviation of both local and remote neuroinflammation, suggesting the promising role of adjuvant ASC therapies for clinical compressive neuropathy.
压迫性神经病变是一种常见的外周神经慢性创伤性损伤，会导致感觉和运动功能出现不同程度的损害。尽管进行了减压手术，但仍有相当一部分患者的临床症状持续存在，10%-25%的病例出现肌肉萎缩和持续性神经病理性疼痛。受损神经中过度的炎症反应和免疫细胞浸润会阻碍轴突再生和功能恢复。虽然脂肪源性干细胞（ASC）已显示出神经再生和免疫调节潜力，但其对压迫性神经病变的具体作用仍不明确。
我们对成年雄性Sprague-Dawley大鼠进行改良的慢性压迫性损伤（CCI）模型，以诱导坐骨神经出现不可逆的神经病理性疼痛和肌肉萎缩。进行神经内ASC注射和神经减压。对受伤神经及相关背根神经节（DRG）进行行为分析、肌肉检查、电生理评估和免疫荧光检查，以探讨轴突再生、神经炎症及炎症基因表达的调节。追踪移植的ASC，以研究其对局部神经和DRG的潜在有益机制。
大鼠坐骨神经慢性缩窄可诱导持续性神经病理性疼痛。局部ASC治疗显示出显著的有益效果，包括缓解机械性异常疼痛、改善步态、肌纤维再生和电生理恢复。此外，局部移植的ASC促进轴突再髓鞘化，减轻神经炎症，并减少受损神经及相关背根神经节（DRG）的炎症细胞浸润。移植的ASC存活和保持表型不到7天，但对受损神经和DRG中炎症基因表达具有强大的免疫调节作用。
局部移植ASC至受压神经可通过减轻局部和远处神经炎症，改善大鼠坐骨神经不可逆慢性缩窄损伤后的感觉和运动恢复，提示辅助ASC治疗在临床压迫性神经病变中具有潜在作用。
