Efficient Strategies for Microglia Replacement in the Central Nervous System
Zhen Xu,
Yanxia Rao,
Yubin Huang,
Tian Zhou,
Rui Feng,
Shanshan Xiong,
Ti-Fei Yuan,
Shan Qin,
Yijie Lu,
Xin Zhou,
Xiaoyu Li,
Bo Qin,
Ying Mao,
Bo Peng
Affiliations
Zhen Xu
Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
Yanxia Rao
Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 201108, China
Yubin Huang
Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
Tian Zhou
Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
Rui Feng
Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
Shanshan Xiong
Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
Ti-Fei Yuan
Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 201108, China
Shan Qin
Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China; Shenzhen Aier Eye Hospital, Shenzhen 518032, China
Yijie Lu
Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China; Shenzhen Aier Eye Hospital, Shenzhen 518032, China
Xin Zhou
Department of Neurosurgery, Huashan Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontier Center for Brain Science, Fudan University, Shanghai 200032, China
Xiaoyu Li
Department of Neurosurgery, Huashan Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontier Center for Brain Science, Fudan University, Shanghai 200032, China; School of Biomedical Engineering, Capital Medical University, Beijing 100069, China
Bo Qin
Shenzhen Aier Eye Hospital, Shenzhen 518032, China
Ying Mao
Department of Neurosurgery, Huashan Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontier Center for Brain Science, Fudan University, Shanghai 200032, China
Bo Peng
Department of Neurosurgery, Huashan Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontier Center for Brain Science, Fudan University, Shanghai 200032, China; Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China; Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu 226001, China; Corresponding author
Summary: Microglia are important immune cells in the central nervous system (CNS). Dysfunctions of gene-deficient microglia contribute to the development and progression of multiple CNS diseases. Microglia replacement by nonself cells has been proposed to treat microglia-associated disorders. However, some attempts have failed due to low replacement efficiency, such as with the traditional bone marrow transplantation approach. In this study, we develop three efficient strategies for microglia replacement: microglia replacement by bone marrow transplantation (mrBMT), microglia replacement by peripheral blood (mrPB), and microglia replacement by microglia transplantation (mrMT). mrBMT and mrPB allow microglia-like cells to efficiently replace resident microglia in the whole CNS. On the other hand, mrMT achieves microglia replacement in brain regions of interest. In summary, the present study offers effective tactics for microglia replacement with diverse application scenarios, which potentially opens up a window on treating microglia-associated CNS disorders.
