State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, No. 163, Xianlin Avenue, Qixia District, Nanjing, 210023, China; Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, 210002, China.
Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, 210002, China.
Biomed Pharmacother. 2021 Jan;133:110981. doi: 10.1016/j.biopha.2020.110981. Epub 2020 Nov 11.
Post-traumatic stress disorder (PTSD) is a mental disorder characterized by hippocampal neuron loss and cognitive dysfunction. The aim of the present study was to investigate the potential functional outcomes of transplantation of induced pluripotent stem cell-derived neural progenitor cells (iPSC-NPCs) for treating PTSD. Human induced pluripotent stem cell (iPSCs), differentiated into neural progenitor cells (NPCs) in vitro, were transplanted into the brain of rat. Following iPSC-NPCs transplantation, cognitive function was determined. The open field test and fear condition test indicated that long-term iPSC-NPCs transplantation ameliorated cognitive dysfunction and reduced freezing time in PTSD rats. Following testing, the brain of rat was analyzed using immunocytochemistry and immunofluorescence. The results revealed that iPSC-NPCs differentiated into neurons replacing the loss of hippocampus neurons, and iPSC-NPCs transplantation showed higher expression of glial fibrillary acidic protein (GFAP) and increased number of NeuN compared with the control group. Moreover, western blot analysis suggested enhanced expression of brain-derived neurotrophic factor (BDNF) in hippocampus tissue of iPSC-NPCs transplanted rats in comparison to the PBS group. Collectively, these findings showed that iPSC-NPCs could promote regeneration and motor function recovery in PTSD model.
创伤后应激障碍（PTSD）是一种以海马神经元丢失和认知功能障碍为特征的精神障碍。本研究旨在探讨诱导多能干细胞衍生的神经祖细胞（iPSC-NPCs）移植治疗 PTSD 的潜在功能结果。将人诱导多能干细胞（iPSCs）在体外分化为神经祖细胞（NPCs），然后移植到大鼠脑内。进行 iPSC-NPC 移植后，确定认知功能。旷场试验和恐惧条件试验表明，长期 iPSC-NPC 移植可改善 PTSD 大鼠的认知功能障碍并减少冻结时间。测试后，使用免疫细胞化学和免疫荧光法分析大鼠的大脑。结果表明，iPSC-NPC 分化为神经元，取代海马神经元的丢失，与对照组相比，iPSC-NPC 移植显示出更高的神经胶质纤维酸性蛋白（GFAP）表达和更多的 NeuN。此外，Western blot 分析表明，与 PBS 组相比，iPSC-NPC 移植大鼠海马组织中脑源性神经营养因子（BDNF）的表达增强。综上所述，这些发现表明，iPSC-NPC 可促进 PTSD 模型中神经元的再生和运动功能的恢复。
