title: Immunosuppression via Loss of IL2rγ Enhances Long-Term Functional Integration of hESC-Derived Photoreceptors in the Mouse Retina.
abstract: 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.
authors.affiliation: Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945-1400, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945-1400, USA.
authors.forename: Helen
authors.initials: H
authors.lastname: Cifuentes
authors.affiliation: Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945-1400, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Reynolds
authors.affiliation: Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945-1400, USA. Electronic address: dlamba@buckinstitute.org.
authors.forename: Deepak A
authors.initials: DA
authors.lastname: Lamba
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001766:Blindness / Q000151:congenital / Q000473:pathology / Q000628:therapy; D002470:Cell Survival / Q000528:radiation effects; D000066449:Human Embryonic Stem Cells / Q000378:metabolism*; D006801:Humans; D007165:Immunosuppression Therapy; D053631:Interleukin Receptor Common gamma Subunit / Q000172:deficiency* / Q000378:metabolism; D008027:Light; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation / Q000235:genetics; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism* / Q000473:pathology* / Q000528:radiation effects; D033581:Stem Cell Transplantation; D013997:Time Factors; D014184:Transplantation, Homologous
chemical_list: D015415:Biomarkers; D053631:Interleukin Receptor Common gamma Subunit
keywords: AMD; Leber congenital amaurosis; c-Fos; iPSC; immune rejection; natural killer cells; pupillary light reflex; retinitis pigmentosa; stem cells; visual function