Schepanski Steven, Ngoumou Gonza B, Buss Claudia, Seifert Georg
Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charité Competence Center for Traditional and Integrative Medicine (CCCTIM), Berlin, Germany.
Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Pediatrics, Division of Oncology and Hematology, Berlin, Germany.
Front Immunol. 2025 Jan 29;16:1538920. doi: 10.3389/fimmu.2025.1538920. eCollection 2025.
This review evaluates models for studying how maternal influences during pregnancy impact the development of offspring microglia, the immune cells of the central nervous system. The models examined include primary microglia cultures, microglia cell lines, iPSC-derived microglia, PBMC-induced microglia-like cells, 3D brain organoids derived from iPSCs, and Hofbauer cells. Each model is assessed for its ability to replicate the environment of the developing brain, with a focus on their strengths, limitations, and practical challenges. Key factors such as scalability, genetic and epigenetic fidelity, and physiological relevance are highlighted. Microglia cell lines are highly scalable but lack genetic and epigenetic fidelity. iPSC-derived microglia provide moderate physiological relevance and patient-specific genetic insights but face operational and epigenetic challenges inherent to reprogramming. 3D brain organoids, derived from iPSCs, offer an advanced platform for studying complex neurodevelopmental processes but require extensive resources and technical expertise. Hofbauer cells, which are fetal macrophages located in the placenta and share a common developmental origin with microglia, are uniquely exposed to prenatal maternal factors and, depending on fetal barrier maturation, exhibit variable epigenetic fidelity. This makes them particularly useful for exploring the impact of maternal influences on fetal programming of microglial development. The review concludes that no single model comprehensively captures all aspects of maternal influences on microglial development, but it offers guidance on selecting the most appropriate model based on specific research objectives and experimental constraints.
本综述评估了用于研究孕期母体影响如何影响后代小胶质细胞（中枢神经系统的免疫细胞）发育的模型。所研究的模型包括原代小胶质细胞培养物、小胶质细胞系、诱导多能干细胞（iPSC）衍生的小胶质细胞、外周血单核细胞（PBMC）诱导的小胶质样细胞、iPSC来源的三维脑类器官和霍夫鲍尔细胞。对每个模型复制发育中大脑环境的能力进行了评估，重点关注其优势、局限性和实际挑战。强调了可扩展性、遗传和表观遗传保真度以及生理相关性等关键因素。小胶质细胞系具有高度可扩展性，但缺乏遗传和表观遗传保真度。iPSC衍生的小胶质细胞具有一定的生理相关性和患者特异性遗传见解，但面临重编程固有的操作和表观遗传挑战。iPSC来源的三维脑类器官为研究复杂的神经发育过程提供了一个先进的平台，但需要大量资源和技术专长。霍夫鲍尔细胞是位于胎盘的胎儿巨噬细胞，与小胶质细胞有共同的发育起源，独特地暴露于产前母体因素，并且根据胎儿屏障成熟情况，表现出可变的表观遗传保真度。这使得它们对于探索母体影响对小胶质细胞发育的胎儿编程的影响特别有用。综述得出结论，没有单一模型能全面涵盖母体对小胶质细胞发育影响的所有方面，但它为根据特定研究目标和实验限制选择最合适的模型提供了指导。
