Guangdong-Hongkong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory, Jinan University, Guangzhou 510632, PR China.
Guangdong-Hongkong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory, Jinan University, Guangzhou 510632, PR China.
Neurosci Lett. 2020 Sep 14;735:135201. doi: 10.1016/j.neulet.2020.135201. Epub 2020 Jun 23.
Spinal cord injury (SCI) is a worldwide problem and transplantation of neural progenitor cells (NPCs) represents a promising treatment strategy. Urine derived induced pluripotent stem cells (UiPSCs) which enable the generation of patient-specific NPCs, provide an invaluable source of autologous cells for future therapeutic applications after SCI. However, the fate and potential contribution of transplanted human UiPSCs-derived NPCs (UiPSC-NPCs) into injured spinal cords remain largely unknown. In this study, using a rat contusive SCI model, we evaluated the survival, migration and differentiation of UiPSC-NPCs after transplantation at subacute phase. Transplanted cells survived and migrated from the site of grafting towards the lesion epicenter. More than 25 % cells survived over 4 weeks post transplantation, with a few of them differentiated into neurons and astrocytes. Cytokine and chemokine levels within the injured spinal cord tissues were measured using multiplex immunoassays to evaluate the immune response. Pro-inflammatory factors and chemokines were significantly decreased at 3 days after UiPSC-NPCs transplantation. At 7 days post transplantation, a lower level of pro-inflammatory factor IFN-γ and a higher level of pro-inflammatory IL-2 were found in UiPSC-NPCs group than in the control. Transplantation of UiPSC-NPCs showed little effect on microglia activation at the lesion epicenter. However, the number of microglia cells at 4 mm rostral to the injury site was significantly decreased. The size of lesion cavity was reduced after transplantation of UiPSC-NPCs. In conclusions, the UiPSC-NPCs transplanted at the subacute phase of SCI showed a beneficial effect on tissue repairing.
脊髓损伤 (SCI) 是一个全球性的问题，神经祖细胞 (NPCs) 的移植代表了一种有前途的治疗策略。尿液衍生的诱导多能干细胞 (UiPSCs) 可以生成患者特异性 NPCs，为 SCI 后的未来治疗应用提供了宝贵的自体细胞来源。然而，移植的人 UiPSCs 衍生 NPCs (UiPSC-NPCs) 进入损伤的脊髓中的命运和潜在贡献在很大程度上仍然未知。在这项研究中，我们使用大鼠挫伤性 SCI 模型，在亚急性阶段评估了移植后 UiPSC-NPCs 的存活、迁移和分化。移植细胞从移植部位向损伤中心迁移和迁移。超过 25%的细胞在移植后 4 周内存活，其中一些分化为神经元和星形胶质细胞。使用多重免疫分析测量损伤脊髓组织中的细胞因子和趋化因子水平，以评估免疫反应。在 UiPSC-NPCs 移植后 3 天，促炎因子和趋化因子显著降低。在移植后 7 天，UiPSC-NPCs 组的促炎因子 IFN-γ 水平较低，促炎因子 IL-2 水平较高。UiPSC-NPCs 移植对损伤中心处的小胶质细胞激活几乎没有影响。然而，在损伤部位前 4 毫米处的小胶质细胞数量明显减少。UiPSC-NPCs 移植后损伤腔的大小减小。总之，在 SCI 的亚急性阶段移植的 UiPSC-NPCs 对组织修复具有有益的作用。
