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Human iPSC-derived microglia

Access a toolkit of functional, consistent in vitro models to study neurodegenerative disease and neuroinflammation

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Microglia, the resident macrophages of the CNS, play critical roles in neural function by regulating neurogenesis, synaptic remodelling, and serving as first responders to infection. Dysregulated microglia activity is highly implicated in the pathology of neurodegenerative diseases, including Alzheimer’s, Parkinson's, and Huntington's disease. 

Studying microglia dysfunction is challenging, as many available models fail to recapitulate human-specific disease phenotypes. Primary human microglia are hard to isolate and vary between donors, immortalised cell lines such as HMC3 are prone to dedifferentiation and genetic drift, and traditional protocols for directed differentiation of hiPSCs are laborious resulting in the production of heterogeneous cultures with high batch-to-batch variability. 

ioMicroglia provides a rapidly maturing, consistent, and functional source of human iPSC-derived microglia, bypassing these limitations. ioMicroglia are ready for experiments within 4 days of thawing and can be easily integrated into multi-cell culture models.

What scientists say about ioMicroglia

An image of Matteo Zanella, PhD

Matteo Zanella, PhD

Associate Research Leader | Charles River

"At Charles River we used bit.bio ioMicroglia in several projects. We are very satisfied with their performances, as they efficiently and robustly recapitulate both morphological and functional properties of microglia cells"

Learn more about ioMicroglia and explore the data

Learn more about ioMicroglia and explore the data

ioMicroglia are ready for experimentation 4 days post-thaw

 

ioMicroglia rapidly acquire a homogeneous microglia phenotype upon thawing, as captured in this 10-day time course. This consistent and rapid maturation provides scientists with confidence in the reproducible generation of functional cultures in just a few days.

HiPSC-derived ioMicroglia overcome functional and phenotypic limitations of the widely-used HMC3 cell line

The HMC3 immortalised cell line has long been a widely used microglial model due to its ease of culture and scalability. However, it has some limitations that compromise its utility for translational research. HMC3 cells lack key microglial identity markers like P2RY12 and TREM2, possess a transcriptomic profile significantly different from primary microglia, and functionally demonstrate very weak or no phagocytic activity and a blunted cytokine response. In contrast, ioMicroglia provide a consistent, phenotypically accurate model, expressing key canonical markers and demonstrating robust phagocytic function and cytokine release profiles. Incorporating this human-relevant model offers a powerful opportunity to de-risk the drug discovery pipeline, filter out false positives, and increase the translational potential of preclinical findings.

Whole transcriptome analysis demonstrates that male donor-derived ioMicroglia are highly similar to primary adult and foetal microglia

ioMicroglia-PCA-plot-compared to Abud

 

ioMicroglia closely mimic the molecular identity of human foetal and adult microglia. They overcome the key limitations of sourcing constraints and donor variability of primary cells as well as the heterogeneity and batch-to-batch inconsistency caused by complex differentiation protocols.

This principal component analysis (PCA) plot of bulk RNA sequencing data validates the transcriptomic identity of ioMicroglia. By integrating male donor-derived ioMicroglia with external data sets from Abud et al1., the analysis reveals that ioMicroglia exhibit a transcriptomic clustering with primary foetal and adult microglia. This demonstrates that ioMicroglia possess a molecular profile highly similar with in vivo human cells, providing an accessible, physiologically relevant model.

ioMicroglia secrete cytokines in response to LPS / IFN-γ and Aβ42 oligomer

ab42 cytokine secretion male and female microglia

 

The cytokine release assay is a valuable tool for ensuring that microglia behave in vitro as they would in vivo. ioMicroglia secrete proinflammatory and anti-inflammatory cytokines (IL-6, TNFα, IL-1β,and IL-8)  in response to stimuli such as Lipopolysaccharides (LPS) and Interferon Gamma (IFN-γ), and amyloidβ-42 (Aβ42).

Female donor-derived ioMicroglia show phagocytic function in co-culture with ioGlutamatergic Neurons

 

ioMicroglia demonstrate robust and selective phagocytic activity while in a 10-day co-culture with ioGlutamatergic Neurons. As captured in this time-lapse, the microglia actively engulf pHrodo Red Zymosan particles without any adverse effects on neuronal morphology, giving scientists confidence in their ability to build stable, functionally validated co-culture models for studying specific glial-neuronal interactions.

bit.bio has optimised protocols for phagocytosis and cytokine release assays, enabling scientists to implement co-culture systems and perform these assays with ease.

ioMicroglia Alzheimer's disease models demonstrate disease-related phenotypes

AB42 Percentage positive- Male WT ApoE (1)

 

ioMicroglia have been engineered with early-onset Alzheimer’s disease mutations in APOE and TREM2 genes, providing a system to study disease-related phenotypes. These models demonstrate robust phagocytic activity against both E. coli and fluorescent Aβ42 particles. Furthermore, the cells exhibit a complex cytokine secretion profile (including IL-6, IL-8, and IL-1β) in response to inflammatory stimuli (LPS/IFN-γ) and Aβ42 oligomers. This consistent, human-relevant model allows scientists to study how risk genotypes modulate core microglial functions.

Quad-culture model recreates complex glial-neuronal interactions for neuroinflammation studies

bit.bio-immunostaining-imaging-of-quad-culture-including-neurons-and-glial cells

 

A quad-culture model integrates ioMicroglia, ioOligodendrocyte-like cells, ioGlutamatergic Neurons, and human iPSC-derived astrocytes, providing a physiological system to investigate the role of glial cells in neurodegenerative disease mechanisms.

A human 3D neuroinflammation model using BrainZell organoids with integrated bit.bio ioMicroglia

BrainZell AppNote Q226

 

Human brain organoids often lack a functional immune component, limiting their ability to capture neuroimmune interactions. This application note demonstrates how integrating ioMicroglia enables a more physiologically relevant human 3D model with measurable inflammatory signalling, cytokine release, and pharmacological modulation.

Utilising GFP ioMicroglia for live-cell imaging and easy co-culture tracking

human-GFP-microglia-iba1-dapi-p2ry12 long

 

ioMicroglia have been engineered to constitutively express green fluorescent protein (GFP), offering scientists a fluorescent human microglia model ideal for co-culture with other neural cell types, enabling effortless tracking in multi-cellular systems.

Constitutive GFP expression throughout the cytosol facilitates live-cell imaging, enabling the assessment of cell motility and visualisation of microglial activation states. GFP-labelled human microglia streamline cell sorting workflows by eliminating the need for antibody staining.

CRISPR-Ready ioMicroglia enables CRISPR knockout screening

Pooled-CRISPR-knockout-screen-in-human-microglia-LPS-stimulation-Heatmap

 

CRISPRko-Ready ioMicroglia enable high-resolution pooled single-cell CRISPR knockout (scCRISPR) screens to systematically map gene function. In a targeted study focused on 110 neurodegeneration-linked genes, cells were transduced and subsequently challenged with LPS to induce a transcriptomic activation signature.

Delivered cryopreserved, the cells are ready for experimentation from 4 days post-thaw

 

In this video, our scientist takes you through the step-by-step process of how to thaw, seed and culture ioMicroglia, which complements our expert scientist's top tips on understanding the dynamic morphology of microglia, handling cells gently, and using the right seeding density and media changes. 

 

Expand your research

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Model diversity with ioMicroglia Female
De-risk compound screening with microglia from diverse backgrounds
Expand your research
Model diversity with ioMicroglia Female
De-risk compound screening with microglia from diverse backgrounds
hIPSC-derived-microglia-multiple-donor-backgrounds

Women are greatly underrepresented in drug development and clinical trials. 
Introducing female-derived cells into the early stage of research and drug discovery can help to better address this disparity.

Key applications for Female ioMicroglia in neurodegeneration drug discovery
- Neuroinflammatory in vitro modelling
- Target ID and validation
- Compound screening 

Discover the data

Co-culture-hiPSC-derived-glutamatergic-neurons-and-microglia
Build disease-relevant in vitro models
Model neurodegenerative disease with microglia-neuron co-cultures
Expand your research
Build disease-relevant in vitro models
Model neurodegenerative disease with microglia-neuron co-cultures
Co-culture-hiPSC-derived-glutamatergic-neurons-and-microglia

Access 20 neuronal disease models and 4 microglia disease models with a single co-culture protocol.

View the co-culture protocol 

Explore ioGlutamatergic Neuron Disease Models 
Explore ioMicroglia Disease Models

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Light up your co-cultures
Track GFP ioMicroglia in complex multi-cell cultures
Expand your research
Light up your co-cultures
Track GFP ioMicroglia in complex multi-cell cultures
Tracking-hiPSC-derived-cells-in-culture

Human iPSC-derived microglia engineered to constitutively express GFP enable easy visualisation, tracking and isolation of cells in complex multi-cell cultures.

Discover the data

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Simplify gene knockouts and CRISPR screens
Have you considered CRISPRko-Ready ioMicroglia?
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Simplify gene knockouts and CRISPR screens
Have you considered CRISPRko-Ready ioMicroglia?
CRISPR-ready-hiPSC-derived-cells-for-functional-genomics

Built from our ioMicroglia Male and engineered to constitutively express Cas9. 
With optimised guide RNA delivery protocols and high knockout efficiency, start measuring readouts from gene knockouts and CRISPR screens within days.
Save months of work by skipping complex cell line engineering and cell differentiation workflows.

Discover the data on CRISPRko-Ready ioMicroglia

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Frequently Asked Questions (FAQs)

  • What is the role of microglia in neurodegenerative disease research?

Microglia are the resident macrophages of the central nervous system (CNS), serving as the primary line of defence against infection and regulating critical homeostatic processes like neurogenesis and synaptic remodelling. The dysregulation of microglial activity plays a pivotal role in the pathogenesis of neurodegenerative disorders, specifically Alzheimer’s, Parkinson’s, and Huntington’s disease.

 

  • How do human iPSC-derived microglia compare with immortalised cell lines?

Immortalised microglial cell lines, such as HMC3, are prone to dedifferentiation and genetic drift, and often lack key microglial identity markers and show weak phagocytic activity. Human iPSC-derived microglia overcome these functional and phenotypic limitations by providing a physiologically relevant model that expresses canonical markers and avoids the instability associated with immortalised lines.

 

  • In what way do ioMicroglia recapitulate human biology in vitro?

ioMicroglia recapitulate the transcriptomic profile of primary human foetal and adult microglia. Bulk RNA sequencing confirms that the gene expression profile of these cells cluster with primary datasets, validating their physiological relevance as a consistent alternative to donor-derived primary cells.

 

  • What functional assays are compatible with human iPSC-derived microglia?

ioMicroglia, human iPSC-derived microglia, are compatible with standard functional assays, most notably phagocytosis and cytokine release screening. These cells demonstrate robust functional maturity by actively phagocytosing targets, such as E. coli and amyloid-beta (Aβ42) and secreting inflammatory cytokines (e.g., IL-6, TNFα) upon stimulation, enabling the precise modelling and quantification of neuroinflammatory states.

 

  • How can human iPSC-derived microglia be used to model genetic risk in Alzheimer’s disease?

ioMicroglia, human iPSC-derived microglia, has been engineered with specific disease-related mutations, such as those found in the TREM2 and APOE genes associated with Alzheimer’s disease. By comparing these disease-relevant mutations to genetically matched wild-type controls, scientists can isolate how specific genotypes drive phenotypic changes, such as altered phagocytosis, in a controlled experimental setup. 

References

  1. Abud E, et al. "iPSC-Derived Human Microglia-like Cells to Study Neurological Diseases." Neuron, 2018; 94(2): 278-293, doi: 10.1016/j.neuron.2017.03.042

  2. Woolf Z,  et al. "In vitro models of microglia: a comparative study." Sci Rep 15, 2025; 15621, https://doi.org/10.1038/s41598-025-99867-z

  3. Lloyd AF, et al. "Deep proteomic analysis of microglia reveals fundamental biological differences between model systems." Cell Reports, 2024. 43, issue 11, doi: 10.1016/j.celrep.2024.114908

  4. Zhou Y., et al. "Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and TREM2-independent cellular responses in Alzheimer's disease." Nat Med, 2020, 26(1):131-142, doi: 10.1038/s41591-019-0695-9