ArticleStem cell research & therapy2021
Submacular integration of hESC-RPE monolayer xenografts in a surgical non-human primate model.
Article in Stem cell research & therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 17 citations in OpenAlex.
- Preclinical quality, safety, and efficacy of a CGMP iPSC-derived myogenic progenitor product for the treatment of muscular dystrophies.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Retinal Pigment Epithelium Transplantation in Retinal Disease: Clinical Trial Development, Challenges, and Future Directions.Biomolecules · 2025Review
- Advances in the study of tissue-engineered retinal pigment epithelial cell sheets.Regenerative therapy · 2024Review
- Advances in retinal pigment epithelial cell transplantation for retinal degenerative diseases.Stem cell research & therapy · 2024Review
- Advances in the engineering of the outer blood-retina barrier: From in-vitro modelling to cellular therapy.Bioactive materials · 2024Review
- Comparison of retinal degeneration treatment with four types of different mesenchymal stem cells, human induced pluripotent stem cells and RPE cells in a rat retinal degeneration model.Journal of translational medicine · 2023Article
- Single-cell transcriptomics reveals maturation of transplanted stem cell-derived retinal pigment epithelial cells toward native state.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Characterizing and Quenching Autofluorescence in Fixed Mouse Adrenal Cortex Tissue.International journal of molecular sciences · 2023Article
- Pan-retinal ganglion cell markers in mice, rats, and rhesus macaques.Zoological research · 2023Article
- Cell maturation influences the ability of hESC-RPE to tolerate cellular stress.Stem cell research & therapy · 2022Article
- Update of application of olfactory ensheathing cells and stem cells/exosomes in the treatment of retinal disorders.Stem cell research & therapy · 2022Review
- A Surgical Kit for Stem Cell-Derived Retinal Pigment Epithelium Transplants: Collection, Transportation, and Subretinal Delivery.Frontiers in cell and developmental biology · 2022Article
Corrections and comments
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Authors and funding
12 authors at 7 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHuman pluripotent stem cells (hPSCs) provide a promising cell source for retinal cell replacement therapy but often lack standardized cell production and live-cell shipment logistics as well as rigorous analyses of surgical procedures for cell transplantation in the delicate macula area. We have previously established a xeno- and feeder cell-free production system for hPSC differentiated retinal pigment epithelial (RPE) cells, and herein, a novel immunosuppressed non-human primate (NHP) model with a disrupted ocular immune privilege is presented for transplanting human embryonic stem cell (hESC)-derived RPE on a scaffold, and the safety and submacular graft integration are assessed. Furthermore, the feasibility of intercontinental shipment of live hESC-RPE is examined.
methodsCynomolgus monkeys were systemically immunosuppressed and implanted with a hESC-RPE monolayer on a permeable polyester-terephthalate (PET) scaffold. Microscope-integrated intraoperative optical coherence tomography (miOCT)-guided surgery, postoperative follow-up incorporated scanning laser ophthalmoscopy, spectral domain (SD-) OCT, and full-field electroretinography (ERG) were used as outcome measures. In addition, histology was performed after a 28-day follow-up.
resultsIntercontinental cell shipment, which took >30 h from the manufacturing to the transplantation site, did not alter the hESC-RPE quality. The submacular hESC-RPE xenotransplantation was performed in 11 macaques. The miOCT typically revealed foveal disruption. ERG showed amplitude and peak time preservation in cases with favorable surgical outcomes. Histology confirmed photoreceptor preservation above the grafts and in vivo phagocytosis by hESC-RPE, albeit evidence of cytoplasmic redistribution of opsin in photoreceptors and glia hypertrophy. The immunosuppression protocol efficiently suppressed retinal T cell infiltration and microglia activation.
conclusionThese results suggest both structural and functional submacular integrations of hESC-RPE xenografts. It is anticipated that surgical technique refinement will further improve the engraftment of macular cell therapeutics with significant translational relevance to improve future clinical trials.
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