Immunosuppression via Loss of IL2rγ Enhances Long-Term Functional Integration of hESC-Derived Photoreceptors in the Mouse Retina

Publication date: Available online 12 January 2017
Source:Cell Stem Cell
Author(s): Jie Zhu, Helen Cifuentes, Joseph Reynolds, Deepak A. Lamba
Loss of photoreceptors is a common endpoint in degenerative retinal diseases. Human pluripotent stem cells provide a potential source for photoreceptor replacement, but, even in mouse models, the efficiency and efficacy of transplantation-based repair remains poor. In this study, we examined the degree to which immune rejection contributes to these disappointing outcomes using an immunodeficient IL2 receptor γ (IL2rγ)-null mouse model. Our results show that prevention of cell rejection in the normal and degenerating retinal environment significantly improves long-term survival and integration of hESC-derived donor retinal cells. Transplanted cells are able to differentiate into mature photoreceptors expressing various opsins and can functionally integrate into congenitally blind mice. Our work suggests that even though the retina is often considered immune-privileged, suppression of host immune-mediated cell rejection may well be a useful approach for improving long-term integration of transplanted cells with a view to successful clinical outcomes.

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Teaser

Lamba and colleagues show that immunosuppression can significantly improve the survival and functional integration of hESC-derived cells into recipient mouse retinas as far out as 9 months, suggesting that immunosuppression may be a useful way to enhance clinical cell transplantation outcomes for patients even in a location traditionally considered immune-privileged.


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