小胶质细胞是存在于中枢神经系统的巨噬细胞,他们在那里进行免疫监视,突触重塑,神经发生,并监测脑损伤或潜在病原体产生的信号。通常,啮齿动物模型用于研究小胶质细胞,因为可用的转基因小鼠系成功完成了特定的遗传操作。然而,人类和啮齿动物的小胶质细胞表现出显著差异,它们反映在不同的形态和功能特性上。这些差异在遗传和转录组学上,而且在信号分子的表达和年龄相关的变化。有几种策略可用于研究人类小胶质细胞,如使用癫痫和肿瘤组织以及死后大脑样本的手术切除。此外,人类诱导的多能干细胞(hPSC)的产生以及将它们分化为小胶质细胞样细胞的可能性为比较啮齿类动物和人脑的小胶质细胞功能提供了独特的机会.使用人类离体和体外脑模型可以研究人类小胶质细胞,模仿体内条件。这将有助于更好地理解人脑中小胶质细胞的真实生活行为和功能。本章旨在强调人类和啮齿动物小胶质细胞之间的显著相似性和差异,以便重新评估不同人脑疾病的小鼠模型。建议使用体外和离体人脑模型。对大脑中活体人类小胶质细胞的研究可能有助于定义与动物模型的差异,并改善临床干预措施以治疗脑部病变,使用替代目标。
Microglia are macrophages residing in the central nervous system, where they perform immune surveillance, synaptic remodeling, neurogenesis, and monitor signals arising from brain injuries or potential pathogens.Commonly, rodent models are used for studying microglia because of the available transgenic mouse lines in which specific genetic manipulations are successfully accomplished. However, human and rodents microglia showed significant differences, which are reflected in different morphological and functional properties. These differences are in genetic and transcriptomic, but also in the expression of signaling molecules and age-associated changes.Several strategies are available to study human microglia, as using surgical brain resections from epileptic and tumoral tissues and from post mortem brain samples. In addition, the generation of human-induced pluripotent stem cells (hPSCs) and the possibility to differentiate them in microglia-like cells provide unique opportunities to compare microglia functions between rodents\' and human brain.The use of human ex vivo and in vitro brain models allows the study of human microglia, mimicking in vivo conditions. This will be useful for a better understanding of the real live behavior and functions of microglia in the human brain. This chapter aims to highlight significant similarities and differences between human and rodent microglia in order to re-evaluate mouse models of different human brain disorders, proposing the use of in vitro and ex vivo human brain models.Studies on living human microglia in the brain may help to define divergences from animal models and to improve clinical interventions to treat brain pathologies, using alternatives targets.