A critical guideline for controlling monocyte-derived macrophages phenotypes

Area of Science:

• Immunology
• Cell Biology

Background:

• Macrophages (Mϕ) are heterogeneous innate immune cells vital for tissue homeostasis, repair, and immune regulation.
• Their plasticity, including polarization into M1/M2 states, is critical but dysregulation contributes to pathologies.
• Studying tissue-resident Mϕ is challenging, leading to the use of monocyte-derived macrophages (MDMs) as an alternative model.

Purpose of the Study:

• To review the principles and limitations of using MDM-based models for studying human macrophage biology.
• To discuss common differentiation protocols for MDMs.
• To propose strategies for enhancing the reproducibility and physiological relevance of macrophage research using MDMs.

Main Methods:

• Literature review of macrophage biology and MDM differentiation protocols.
• Analysis of challenges in studying tissue-resident macrophages.
• Discussion of methodological strategies for improving MDM models.

Main Results:

• MDMs offer a controllable in vitro system for modeling Mϕ biology but differ from tissue-resident counterparts.
• Various differentiation protocols exist, each with specific outcomes.
• Technical challenges limit the study of tissue-resident Mϕ, impacting research reproducibility.

Conclusions:

• MDM models are valuable but require careful consideration of their limitations.
• Standardizing differentiation protocols and implementing advanced techniques can improve MDM model relevance.
• Enhanced MDM models are crucial for advancing our understanding of macrophage functions in health and disease.