Chronic spinal cord injury (SCI) is a devastating medical condition. In the acute phase after injury, there is cell loss resulting in chronic axonal damage and loss of sensory and motor function including loss of oligodendrocytes that results in demyelination of axons and further dysfunction. In the chronic phase, the inhibitory environment within the lesion including the glial scar can arrest axonal growth and regeneration and can also potentially affect transplanted cells. We hypothesized that glial scar ablation (GSA) along with cell transplantation may be required as a combinatorial therapy to achieve functional recovery, and therefore we proposed to examine the survival and fate of human induced pluripotent stem cell (iPSC) derived pre-oligodendrocyte progenitor cells (pre-OPCs) transplanted in a model of chronic SCI, whether this was affected by GSA, and whether this combination of treatments would result in functional recovery. In this study, chronically injured athymic nude (ATN) rats were allocated to one of three treatment groups: GSA only, pre-OPCs only, or GSA+pre-OPCs. We found that human iPSC derived pre-OPCs were multi-potent and retained the ability to differentiate into mainly oligodendrocytes or neurons when transplanted into the chronically injured spinal cords of rats. Twelve weeks after cell transplantation, we observed that more of the transplanted cells differentiated into oligodendrocytes when the glial scar was ablated compared with no GSA. Further, we also observed that a higher percentage of transplanted cells differentiated into V2a interneurons and motor neurons in the pre-OPCs only group when compared with GSA+pre-OPCs. This suggests that the local environment created by ablation of the glial scar may have a significant effect on the fate of cells transplanted into the injury site.

中文翻译：

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在胶质瘢痕消融后慢性损伤脊髓大鼠模型中移植后，区域特异性人前少突胶质细胞产生少突胶质细胞和神经元

慢性脊髓损伤 (SCI) 是一种毁灭性的疾病。在损伤后的急性期，细胞丢失导致慢性轴突损伤和感觉和运动功能丧失，包括导致轴突脱髓鞘和进一步功能障碍的少突胶质细胞丢失。在慢性期，包括胶质瘢痕在内的病变内的抑制环境可以阻止轴突的生长和再生，并且还可能影响移植细胞。我们假设可能需要胶质瘢痕消融 (GSA) 和细胞移植作为实现功能恢复的组合疗法，因此我们建议检查人类诱导多能干细胞 (iPSC) 衍生的前少突胶质祖细胞的存活和命运(pre-OPCs) 移植到慢性 SCI 模型中，这是否受到 GSA 的影响，以及这种治疗组合是否会导致功能恢复。在这项研究中，慢性损伤的无胸腺裸 (ATN) 大鼠被分配到三个治疗组之一：仅 GSA、仅 pre-OPCs 或 GS​​A+pre-OPCs。我们发现人类 iPSC 衍生的前 OPCs 是多效的，当移植到大鼠慢性损伤的脊髓中时，它保留了主要分化为少突胶质细胞或神经元的能力。细胞移植 12 周后，我们观察到与没有 GSA 相比，当胶质瘢痕被消融时，更多的移植细胞分化成少突胶质细胞。此外，我们还观察到，与 GSA+pre-OPCs 相比，仅 pre-OPCs 组中更高百分比的移植细胞分化为 V2a 中间神经元和运动神经元。