Zhang Hongyan, Liu Jingjing, Chen Beike, Chen Xin, Wei Shijun, Zhang Guanghui, Yan Xiaomin, Xue Xingsen, He Guangjian, Lin Jiangkai, Feng Hua, Chu Weihua
Department of Neurosurgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China.
Chongqing Stem Cell and Neural Regeneration Engineering Technology Research Center, Chongqing, 508216, China.
Mol Neurobiol. 2025 Apr;62(4):4617-4630. doi: 10.1007/s12035-024-04539-0. Epub 2024 Oct 29.
Spinal cord injury (SCI) is a catastrophic nerve injury caused by extremely severe damage to the spinal cord, for which effective treatments are currently unavailable. Human amniotic epithelial stem cells (hAESCs) are considered promising candidates for transplantation in various clinical and preclinical applications, due to their lack of limitations such as ethical barriers, immune rejection, tumorigenicity, or cell origin. Nevertheless, the effectiveness and mechanism by which hAESCs treat SCI remain elusive. To assess the motor function recovery process following SCI in rats, the Basso Beattie Bresnahan (BBB) behavior test, inclined plate scale and motor evoked potential (MEP) analysis were used in this study after transplantation of hAESCs at different doses. And the underlying mechanism was investigated by histological and molecular methods. The transplantation of hAESCs can significantly promote the recovery of motor function in SCI group, and the higher the dose, the better the effect. Compared with SCI group, hAESCs group had reduced tissue damage, significantly increased the number of neurons, neurofilaments and myelin sheath, and significantly reduced syringomyelia and glial scars. In addition, hAESCs inhibited the Levels of tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) and increased the expression of the interleukin-4 (IL-4), interleukin-10 (IL-10) and interleukin-13 (IL-13), and promoted the shift of M1-polarized macrophages to M2-polarized macrophages. Our results demonstrate that hAESCs promoted the recovery of motor function after SCI by promoting M2 polarization of macrophages and reducing neuroinflammation. These findings may provide novel therapeutic strategies for SCI.
脊髓损伤（SCI）是一种由脊髓极其严重损伤导致的灾难性神经损伤，目前尚无有效的治疗方法。人羊膜上皮干细胞（hAESCs）因其不存在伦理障碍、免疫排斥、致瘤性或细胞来源等限制，被认为是各种临床和临床前应用中移植的有前景的候选细胞。然而，hAESCs治疗SCI的有效性和机制仍不明确。为了评估大鼠SCI后运动功能恢复过程，本研究在不同剂量hAESCs移植后采用了Basso Beattie Bresnahan（BBB）行为测试、斜板评分和运动诱发电位（MEP）分析。并通过组织学和分子方法研究其潜在机制。hAESCs移植可显著促进SCI组运动功能恢复，且剂量越高效果越好。与SCI组相比，hAESCs组组织损伤减轻，神经元、神经丝和髓鞘数量显著增加，脊髓空洞症和胶质瘢痕显著减少。此外，hAESCs抑制肿瘤坏死因子（TNF-α）和白细胞介素-6（IL-6）水平，增加白细胞介素-4（IL-4）、白细胞介素-10（IL-10）和白细胞介素-13（IL-13）的表达，并促进M1极化巨噬细胞向M2极化巨噬细胞转变。我们的结果表明，hAESCs通过促进巨噬细胞的M2极化和减轻神经炎症促进SCI后运动功能恢复。这些发现可能为SCI提供新的治疗策略。
