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Updated: Sep 11, 2025
Production and Characterization of Human Macrophages from Pluripotent Stem Cells
Published on: April 16, 2020
iPSC-derived macrophages: An in vitro model to study human disease-relevant macrophage biology
Julia Sauer1, Daniela Schloesser2, Katja Koeppen2
1Boehringer Ingelheim Pharma GmbH & Co KG, Biberach an der Riss 88397, Germany.
Abstract:
Human macrophages differ from their mouse counterparts in multiple metabolic pathways, surface protein expression, and transcription factor biology. Monocyte-derived macrophages (MDMs) from blood are generally used to study human macrophage biology in vitro. However, the use of MDMs as a human macrophage model is limited by donor-to-donor variability, total cell availability, preactivation effects, and relative resistance to genetic manipulation. Here, we explored stem cell-derived macrophages to study in vitro disease-relevant macrophage phenotypes. We compared induced pluripotent stem cell-derived macrophages (iDMs) with primary human stem cell-derived macrophages from cord blood-derived macrophages or bone marrow-derived macrophages (BMDMs) in their ability to elaborate tissue and disease-relevant phenotypes in comparison with conventional blood MDMs. Analyses of phenotypical and functional features revealed that iDMs were highly similar to cord blood-derived macrophages and BMDMs, and resembled MDMs. Importantly, all macrophages, and particularly iDMs adopted expected disease-relevant phenotypes in vitro when stimulated with disease-associated mediators. RNA sequencing analyses of in vitro macrophages stimulated with tissue relevant factors revealed that their transcriptomes mapped to human in vivo inflammatory conditions. Using this approach, we found a close correlation between stimulation and expected disease-association counterpart in vivo. In conclusion, we established a streamlined system to link stem cell-derived macrophage phenotypes to relevant macrophage phenotypes in disease states. Thus, enabling conditions for in vitro replication of complex human macrophage biology observed in single-cell RNA sequencing from human diseased tissue.
Insights
Stem cell-derived macrophages, including induced pluripotent stem cell-derived macrophages (iDMs), effectively model human macrophage biology in vitro. These iDMs mimic primary macrophages and adopt disease-relevant phenotypes, aiding research into human inflammatory conditions.
Area of Science:
- Immunology
- Stem Cell Biology
- Macrophage Biology
Background:
- Human macrophages are crucial immune cells, but in vitro studies using primary monocyte-derived macrophages (MDMs) face limitations like donor variability and limited cell availability.
- Existing models struggle with genetic manipulation and replicating complex in vivo macrophage behaviors relevant to disease.
Purpose of the Study:
- To explore the utility of stem cell-derived macrophages, specifically induced pluripotent stem cell-derived macrophages (iDMs), for studying in vitro disease-relevant macrophage phenotypes.
- To compare iDMs with primary stem cell-derived macrophages (from cord blood and bone marrow) and conventional MDMs.
Main Methods:
- Phenotypical and functional analyses of iDMs, cord blood-derived macrophages, bone marrow-derived macrophages (BMDMs), and MDMs.
- Stimulation of in vitro macrophages with disease-associated mediators and tissue-relevant factors.
- RNA sequencing to analyze transcriptomes and compare with in vivo human inflammatory conditions.
Main Results:
- iDMs exhibited high similarity to cord blood-derived macrophages and BMDMs, and resembled MDMs in phenotypical and functional features.
- All tested macrophages, especially iDMs, adopted expected disease-relevant phenotypes upon stimulation with disease-associated mediators in vitro.
- Transcriptome analyses revealed a strong correlation between in vitro stimulated macrophage responses and in vivo human inflammatory conditions.
Conclusions:
- A streamlined system was established to link stem cell-derived macrophage phenotypes to relevant macrophage phenotypes in disease states.
- This approach enables in vitro replication of complex human macrophage biology observed in diseased tissues, facilitating disease modeling and drug discovery.
