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

Chichagova, Valeria, Georgiou, Maria, Carter, Madeleine, Dorgau, Birthe, Hilgen, Gerrit, Collin, Joseph, Queen, Rachel, Chung, Git, Ajeian, Jila, Moya‐Molina, Marina, Kustermann, Stefan, Pognan, Francois, Hewitt, Philip, Schmitt, Michael, Sernagor, Evelyne, Armstrong, Lyle and Lako, Majlinda (2023) Incorporating microglia‐like cells in human induced pluripotent stem cell‐derived retinal organoids. Journal of Cellular and Molecular Medicine. pp. 1-11. ISSN 1582-1838 (In Press)

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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.

Item Type: Article
Additional Information: Funding information: This work was funded by CRACKIT23 challenge award (NC/CO16206/1), BB/T004460/1 and MR/S035826/1 grants. The authors are grateful to Dr. Kathryn White and Tracey Davey from Newcastle University for help with the TEM analysis. The authors thank Rhea Guerra for assistance with microglial differentiations.
Uncontrolled Keywords: immunocompetent, induced pluripotent stem cell, microglia, retinal organoids
Subjects: C700 Molecular Biology, Biophysics and Biochemistry
Department: Faculties > Health and Life Sciences > Applied Sciences
Depositing User: Elena Carlaw
Date Deposited: 18 Jan 2023 15:21
Last Modified: 18 Jan 2023 15:30

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