Assessing in-vitro models for microglial development and fetal programming: a critical review

Area of Science:

• Neuroscience
• Developmental Biology
• Immunology

Background:

• Maternal factors during pregnancy significantly influence offspring neurodevelopment.
• Microglia, the central nervous system's immune cells, are critical for brain development and function.
• Understanding how prenatal exposures affect microglial development is crucial for identifying risks of neurodevelopmental disorders.

Purpose of the Study:

• To review and evaluate various in-vitro models for studying maternal influences on offspring microglia development.
• To assess the strengths, limitations, and practical applicability of each model.
• To provide guidance for selecting appropriate models based on research objectives.

Main Methods:

• Systematic review of in-vitro models including primary microglia cultures, cell lines, iPSC-derived microglia, PBMC-induced microglia-like cells, 3D brain organoids, and Hofbauer cells.
• Evaluation of models based on scalability, genetic/epigenetic fidelity, and physiological relevance to the in-vivo developing brain.
• Analysis of each model's ability to replicate prenatal maternal influences on microglia.

Main Results:

• Microglia cell lines offer scalability but lack genetic/epigenetic accuracy.
• iPSC-derived microglia provide patient-specific data but have reprogramming-related challenges.
• 3D brain organoids offer complexity but demand significant resources.
• Hofbauer cells, due to their unique placental location, are valuable for studying maternal programming of microglia.

Conclusions:

• No single in-vitro model fully recapitulates maternal influences on microglia development.
• The choice of model depends on specific research questions and experimental constraints.
• Hofbauer cells present a promising avenue for investigating prenatal maternal effects on microglial programming.