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Updated: Aug 14, 2025
Generation of Human Microglia to Combine Them with Retinal Organoids for Improved Disease Modeling
Published on: July 26, 2024
Incorporating microglia-like cells in human induced pluripotent stem cell-derived retinal organoids
Valeria Chichagova1, Maria Georgiou2, Madeleine Carter2
1Newcells Biotech, Newcastle upon Tyne, UK.
Abstract:
Microglia are the primary resident immune cells in the retina. They regulate neuronal survival and synaptic pruning making them essential for normal development. Following injury, they mediate adaptive responses and under pathological conditions they can trigger neurodegeneration exacerbating the effect of a disease. Retinal organoids derived from human induced pluripotent stem cells (hiPSCs) are increasingly being used for a range of applications, including disease modelling, development of new therapies and in the study of retinogenesis. Despite many similarities to the retinas developed in vivo, they lack some key physiological features, including immune cells. We engineered an hiPSC co-culture system containing retinal organoids and microglia-like (iMG) cells and tested their retinal invasion capacity and function. We incorporated iMG into retinal organoids at 13 weeks and tested their effect on function and development at 15 and 22 weeks of differentiation. Our key findings showed that iMG cells were able to respond to endotoxin challenge in monocultures and when co-cultured with the organoids. We show that retinal organoids developed normally and retained their ability to generate spiking activity in response to light. Thus, this new co-culture immunocompetent in vitro retinal model provides a platform with greater relevance to the in vivo human retina.
Insights
Researchers developed a new immunocompetent retinal organoid model by co-culturing human induced pluripotent stem cell-derived retinal organoids with microglia-like cells. This model better mimics the human retina
Area of Science:
- Neuroscience
- Stem Cell Biology
- Immunology
Background:
- Microglia are crucial retinal immune cells regulating neuronal survival and synaptic pruning.
- Pathological conditions involving microglia can exacerbate neurodegeneration.
- Current human induced pluripotent stem cell (hiPSC)-derived retinal organoids lack immune cells, limiting their physiological relevance.
Purpose of the Study:
- To engineer an immunocompetent in vitro retinal model using hiPSC-derived retinal organoids and microglia-like (iMG) cells.
- To assess the capacity of iMG cells to invade and integrate functionally within retinal organoids.
- To evaluate the impact of iMG co-culture on retinal organoid development and function.
Main Methods:
- Co-culture of hiPSC-derived retinal organoids with iMG cells starting at 13 weeks of differentiation.
- Assessment of iMG cell response to endotoxin challenge in monocultures and co-cultures.
- Evaluation of retinal organoid development and light-evoked spiking activity at 15 and 22 weeks.
Main Results:
- iMG cells demonstrated responsiveness to endotoxin challenge both alone and within retinal organoids.
- Retinal organoids in co-culture maintained normal development.
- The co-culture system preserved the light-responsive spiking activity of retinal organoids.
Conclusions:
- The developed hiPSC co-culture system successfully integrates microglia-like cells into retinal organoids.
- This immunocompetent in vitro retinal model exhibits enhanced functional and developmental relevance to the in vivo human retina.
- This model offers a valuable platform for studying retinal immunity, disease, and therapeutic development.
