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Review
. 2025 Aug 20:16:1640935.
doi: 10.3389/fimmu.2025.1640935. eCollection 2025.

Comprehensive review of macrophage models: primary cells and immortalized lines across species

Affiliations
Review

Comprehensive review of macrophage models: primary cells and immortalized lines across species

Tiansong Ding et al. Front Immunol. .

Abstract

In order to preserve homeostasis, macrophages-phagocytic innate immune cells-interact with different tissue types, modulating immunological responses and secreting a variety of cytokines. They are extensively dispersed throughout the body's tissues and organs. Based on their developmental origins, tissue-resident macrophages (TRMs) in humans can be classified into those of embryonic origin and those derived from bone marrow-derived monocytes (BMDMs); embryonically derived macrophages emerge during early development, possess self-renewal capacity, and persist into adulthood in specific tissues such as microglia in the brain and Kupffer cells in the liver, whereas BMDMs originate from hematopoietic stem cells in the bone marrow via monocytic differentiation, infiltrate tissues during inflammation or injury, and differentiate into macrophages that transiently reside in tissues but lack self-renewal capability, thus requiring continuous replenishment. Because of their flexibility and diversity, macrophages participate in a variety of physiological and pathological processes by changing phenotypically and functionally in response to microenvironmental stimuli. This process is known as macrophage polarization. As a consequence, macrophage cultivation in vitro has emerged as a crucial biological technique for mimicking the microenvironment of different disease models. Primary macrophage models and immortalized macrophage models are two distinct types of macrophage models, each with unique origins, functions, benefits, and drawbacks. The features, advantages, disadvantages, isolation procedures, and differentiation induction techniques of primary and immortalized macrophage models are compiled in this review. It also works at the differences between various macrophage cell lines in an effort to shed light on the pathophysiology of inflammatory disorders, viral infection processes, and macrophage immunoregulatory roles.

Keywords: cell models; cross-species; immortalized macrophage cell lines; macrophages; primary macrophages.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Primary macrophages. (A) Undergoes spontaneous differentiation without artificial induction. (B) Requires artificial induction of differentiation.
Figure 2
Figure 2
Immortalized macrophage cell lines.

References

    1. Tauber AI. Metchnikoff and the phagocytosis theory. Nat Rev Mol Cell Biol. (2003) 4:897–901. doi: 10.1038/nrm1244, PMID: - DOI - PubMed
    1. Cuadros MA, Coltey P, Carmen Nieto M, Martin C. Demonstration of a phagocytic cell system belonging to the hemopoietic lineage and originating from the yolk sac in the early avian embryo. Development. (1992) 115:157–68. doi: 10.1242/dev.115.1.157, PMID: - DOI - PubMed
    1. Naito M, Yamamura F, Nishikawa S, Takahashi K. Development, differentiation, and maturation of fetal mouse yolk sac macrophages in cultures. J Leukoc Biol. (1989) 46:1–10. doi: 10.1002/jlb.46.1.1, PMID: - DOI - PubMed
    1. Shapouri-Moghaddam A, Mohammadian S, Vazini H, Taghadosi M, Esmaeili SA, Mardani F, et al. Macrophage plasticity, polarization, and function in health and disease. J Cell Physiol. (2018) 233:6425–40. doi: 10.1002/jcp.26429, PMID: - DOI - PubMed
    1. Sica A, Mantovani A. Macrophage plasticity and polarization: in vivo veritas. J Clin Invest. (2012) 122:787–95. doi: 10.1172/JCI59643, PMID: - DOI - PMC - PubMed

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