State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China.
State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, 19 Xinjiekou Wai Street, Beijing 100875, China.
Stem Cell Reports. 2019 Dec 10;13(6):1022-1037. doi: 10.1016/j.stemcr.2019.10.012. Epub 2019 Nov 21.
Alzheimer's disease (AD) is characterized by memory impairments in its earliest clinical phase. The synaptic loss and dysfunction leading to failures of synaptic networks in AD brain directly cause cognitive deficits of patient. However, it remains unclear whether the synaptic networks in AD brain could be repaired. In this study, we generated functional human induced neural progenitor/stem cells (iNPCs) that had been transplanted into the hippocampus of immunodeficient wild-type and AD mice. The grafted human iNPCs efficiently differentiated into neurons that displayed long-term survival, progressively acquired mature membrane properties, formed graft-host synaptic connections with mouse neurons and functionally integrated into local synaptic circuits, which eventually reinforced and repaired the neural networks of host hippocampus. Consequently, AD mice with human iNPCs exhibited enhanced synaptic plasticity and improved cognitive abilities. Together, our results suggest that restoring synaptic failures by stem cells might provide new directions for the development of novel treatments for human AD.
阿尔茨海默病（AD）的特征是在其最早的临床阶段出现记忆障碍。AD 大脑中导致突触网络失败的突触丧失和功能障碍直接导致患者的认知缺陷。然而，AD 大脑中的突触网络是否可以修复仍不清楚。在这项研究中，我们生成了功能性的人诱导神经祖细胞/干细胞（iNPC），并将其移植到免疫缺陷型野生型和 AD 小鼠的海马体中。移植的人 iNPC 有效地分化为神经元，这些神经元具有长期存活、逐渐获得成熟的膜特性、与小鼠神经元形成移植-宿主突触连接，并在局部突触回路中发挥功能整合，最终增强和修复了宿主海马体的神经网络。结果，接受人 iNPC 移植的 AD 小鼠表现出增强的突触可塑性和改善的认知能力。总之，我们的研究结果表明，通过干细胞恢复突触功能障碍可能为人类 AD 的新型治疗方法的开发提供新的方向。
