Assessing in-vitro models for microglial development and fetal programming: a critical review
This review evaluates in-vitro 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-induce...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1538920/full |
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| author | Steven Schepanski Steven Schepanski Gonza B. Ngoumou Gonza B. Ngoumou Claudia Buss Claudia Buss Claudia Buss Claudia Buss Georg Seifert Georg Seifert |
| author_facet | Steven Schepanski Steven Schepanski Gonza B. Ngoumou Gonza B. Ngoumou Claudia Buss Claudia Buss Claudia Buss Claudia Buss Georg Seifert Georg Seifert |
| author_sort | Steven Schepanski |
| collection | DOAJ |
| description | This review evaluates in-vitro 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 in-vivo 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. |
| format | Article |
| id | doaj-art-b45b4398e31446d8ae438a79d61475ed |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-b45b4398e31446d8ae438a79d61475ed2025-01-29T06:46:20ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011610.3389/fimmu.2025.15389201538920Assessing in-vitro models for microglial development and fetal programming: a critical reviewSteven Schepanski0Steven Schepanski1Gonza B. Ngoumou2Gonza B. Ngoumou3Claudia Buss4Claudia Buss5Claudia Buss6Claudia Buss7Georg Seifert8Georg Seifert9Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charité Competence Center for Traditional and Integrative Medicine (CCCTIM), Berlin, GermanyCharité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Pediatrics, Division of Oncology and Hematology, Berlin, GermanyCharité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charité Competence Center for Traditional and Integrative Medicine (CCCTIM), Berlin, GermanyCharité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Pediatrics, Division of Oncology and Hematology, Berlin, GermanyCharité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Institute of Medical Psychology, Berlin, GermanyUniversity of California, Irvine, Development, Health and Disease Research Program, Irvine, CA, United StatesGerman Center for Child and Adolescent Health (DZKJ), Partner Site Berlin, Charité - Universitätsmedizin Berlin, Berlin, GermanyGerman Center for Mental Health (DZPG), Partner Site Berlin, Charité - Universitätsmedizin Berlin, Berlin, GermanyCharité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charité Competence Center for Traditional and Integrative Medicine (CCCTIM), Berlin, GermanyCharité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Pediatrics, Division of Oncology and Hematology, Berlin, GermanyThis review evaluates in-vitro 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 in-vivo 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.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1538920/fullmicrogliabrain developmentin-vitro modelsneuroimmunology and microglianeurodevelopmental disordersneuropsychiatry |
| spellingShingle | Steven Schepanski Steven Schepanski Gonza B. Ngoumou Gonza B. Ngoumou Claudia Buss Claudia Buss Claudia Buss Claudia Buss Georg Seifert Georg Seifert Assessing in-vitro models for microglial development and fetal programming: a critical review Frontiers in Immunology microglia brain development in-vitro models neuroimmunology and microglia neurodevelopmental disorders neuropsychiatry |
| title | Assessing in-vitro models for microglial development and fetal programming: a critical review |
| title_full | Assessing in-vitro models for microglial development and fetal programming: a critical review |
| title_fullStr | Assessing in-vitro models for microglial development and fetal programming: a critical review |
| title_full_unstemmed | Assessing in-vitro models for microglial development and fetal programming: a critical review |
| title_short | Assessing in-vitro models for microglial development and fetal programming: a critical review |
| title_sort | assessing in vitro models for microglial development and fetal programming a critical review |
| topic | microglia brain development in-vitro models neuroimmunology and microglia neurodevelopmental disorders neuropsychiatry |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1538920/full |
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