Journal
STEM CELL REPORTS
Volume 16, Issue 4, Pages 851-867Publisher
CELL PRESS
DOI: 10.1016/j.stemcr.2021.02.021
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- JapanAgency for MedicalResearch and Development (Japan) [JP20bm0204002]
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Research has shown that hESC- and iPSC-derived retinas express low levels of HLA-I and minimal HLA-II in vitro, possess the ability to suppress immune activation of lymphocytes in co-culture, and partially suppress activated immune cells via the transforming growth factor β signaling pathway. These findings support the potential use of allogeneic hESC- and iPSC-derived retinal transplantation in future clinical applications.
ESC- and iPSC-derived retinal transplantation is a promising therapeutic approach for disease with end-stage retinal degeneration, such as retinitis pigmentosa and age-related macular degeneration. We previously showed medium- to long-term survival, maturation, and light response of transplanted human ESC- and iPSC-retina in mouse, rat, and monkey models of end-stage retinal degeneration. Because the use of patient hiPSC-derived retina with a disease-causing gene mutation is not appropriate for therapeutic use, allogeneic transplantation using retinal tissue/cells differentiated from a stocked hESC and iPSC line would be most practical. Here, we characterize the immunological properties of hESC- and iPSC-retina and present their three major advantages: (1) hESC- and iPSC-retina expressed low levels of human leukocyte antigen (HLA) class I and little HLA class II in vitro, (2) hESC- and iPSC-retina greatly suppressed immune activation of lymphocytes in co-culture, and (3) hESC- and iPSC-retina suppressed activated immune cells partially via transforming growth factor b signaling. These results support the use of allogeneic hESC- and iPSC-retina in future clinical application.
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