Incorporating microglia-like cells in human induced pluripotent stem cell-derived retinal organoids

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.