Rao Yanxia, Peng Bo
Department of Laboratory Animal Science, MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200032, China.
Department of Neurosurgery, Huashan Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, MOE Innovative Center for New Drug Development of Immune Inflammatory Diseases, Fudan University, Shanghai 200000, China.
Fundam Res. 2023 Mar 27;4(2):237-245. doi: 10.1016/j.fmre.2023.02.025. eCollection 2024 Mar.
Microglia are resident immune cells in the central nervous system (CNS) that play vital roles in CNS development, homeostasis and disease pathogenesis. Genetic defects in microglia lead to microglial dysfunction, which in turn leads to neurological disorders. The correction of the specific genetic defects in microglia in these disorders can lead to therapeutic effects. Traditional genetic defect correction approaches are dependent on viral vector-based genetic defect corrections. However, the viruses used in these approaches, including adeno-associated viruses, lentiviruses and retroviruses, do not primarily target microglia; therefore, viral vector-based genetic defect corrections are ineffective in microglia. Microglia replacement is a novel approach to correct microglial genetic defects via replacing microglia of genetic defects with allogenic healthy microglia. In this paper, we systematically review the history, rationale and therapeutic perspectives of microglia replacement, which would be a novel strategy for treating CNS disorders.
小胶质细胞是中枢神经系统（CNS）中的常驻免疫细胞，在中枢神经系统发育、稳态和疾病发病机制中发挥着至关重要的作用。小胶质细胞的基因缺陷会导致小胶质细胞功能障碍，进而导致神经疾病。纠正这些疾病中小胶质细胞的特定基因缺陷可产生治疗效果。传统的基因缺陷纠正方法依赖于基于病毒载体的基因缺陷纠正。然而，这些方法中使用的病毒，包括腺相关病毒、慢病毒和逆转录病毒，并非主要靶向小胶质细胞；因此，基于病毒载体的基因缺陷纠正在小胶质细胞中无效。小胶质细胞替代是一种通过用同种异体健康小胶质细胞替代有基因缺陷的小胶质细胞来纠正小胶质细胞基因缺陷的新方法。在本文中，我们系统地回顾了小胶质细胞替代的历史、原理和治疗前景，这将是一种治疗中枢神经系统疾病的新策略。
