PDF(Pubmed)
Abstract：
BACKGROUND: Spinal cord injury (SCI) is a serious clinical condition that has pathological changes such as increased neuroinflammation and nerve tissue damage, which eventually manifests as fibrosis of the injured segment and the development of a spinal cord cavity leading to loss of function. Cell-based therapy, such as mesenchymal stem cells (MSCs) and neural stem cells (NSCs) are promising treatment strategies for spinal cord injury via immunological regulation and neural replacement respectively. However, therapeutic efficacy is rare reported on combined transplantation of MSC and NSC in acute mice spinal cord injury even the potential reinforcement might be foreseen. Therefore, this study was conducted to investigate the safety and efficacy of co-transplanting of MSC and NSC sheets into an SCI mice model on the locomotor function and pathological changes of injured spinal cord.
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.
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.
摘要：
背景：脊髓损伤（SCI）是一种严重的临床疾病，具有诸如神经炎症和神经组织损伤增加等病理变化，最终表现为损伤节段的纤维化和脊髓腔的发展，导致功能丧失。基于细胞的治疗，如间充质干细胞（MSCs）和神经干细胞（NSCs）分别通过免疫调节和神经替代治疗脊髓损伤是有前景的治疗策略。然而,在急性小鼠脊髓损伤中，MSC和NSC联合移植的治疗效果很少见，即使可以预见潜在的增强作用。因此,本研究旨在探讨将MSC和NSC片联合移植到SCI小鼠模型中对损伤脊髓运动功能和病理变化的安全性和有效性。
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。
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。
