METHODS: To evaluate the therapeutic effects of combination cells, acute SCI mice model were established and combined transplantation of hiPSC-NSCs and hMSCs into the lesion site immediately after the injury. Basso mouse scale was used to perform the open-field tests of hind limb motor function at days post-operation (dpo) 1, 3, 5, and 7 after SCI and every week after surgery. Spinal cord and serum samples were collected at dpo 7, 14, and 28 to detect inflammatory and neurotrophic factors. Hematoxylin-eosin (H&E) staining, masson staining and transmission electron microscopy were used to evaluate the morphological changes, fibrosis area and ultrastructure of the spinal cord.
RESULTS: M&N transplantation reduced fibrosis formation and the inflammation level while promoting the secretion of nerve growth factor and brain-derived neurotrophic factor. We observed significant reduction in damaged tissue and cavity area, with dramatic improvement in the M&N group. Compared with the Con group, the M&N group exhibited significantly improved behaviors, particularly limb coordination.
CONCLUSIONS: Combined transplantation of hiPSC-NSC and hMSC could significantly ameliorate neuroinflammation, promote neuroregeneration, and decrease spinal fibrosis degree in safe and effective pattern, which would be indicated as a novel potential cell treatment option.
方法:为了评估联合细胞的治疗效果,建立急性SCI小鼠模型,并在损伤后立即将hiPSC-NSCs和hMSCs联合移植到病变部位。使用Basso小鼠量表在SCI术后1、3、5和7天以及手术后每周进行后肢运动功能的开放视野测试。在dpo7、14和28时收集脊髓和血清样品以检测炎症和神经营养因子。苏木精-伊红(H&E)染色,masson染色和透射电镜用于评估形态学变化,脊髓的纤维化面积和超微结构。
结果:M&N移植在促进神经生长因子和脑源性神经营养因子分泌的同时,减少了纤维化形成和炎症水平。我们观察到受损组织和空腔面积显著减少,随着M&N集团的戏剧性改善。与Con组相比,M&N组表现出显著改善的行为,尤其是肢体协调。
结论:hiPSC-NSC和hMSC联合移植可显著改善神经炎症,促进神经再生,以安全有效的方式降低脊柱纤维化程度,这将被认为是一种新的潜在细胞治疗选择。