ArticleStem cell research & therapy2025
Effect of immunosuppression on hESC-derived retina organoids in vitro and in vivo.
Article in Stem cell research & therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
6 citing papers in PubMed.
- Photoreceptor replacement: a disease-agnostic approach for the treatment of advanced retinal degeneration.Eye (London, England) · 2026Review
- Generation of a New Immunodeficient Rat Model of Retinal Degeneration With LSL TdTomato Reporter and TdTomato-Pcp2 Expression.Translational vision science & technology · 2026Article
- Redefining ocular safety assessment: retinal organoids as platforms for predicting human ocular toxicology.Genes & genomics · 2026Review
- Next-Generation Strategies for Neural Repair and Regeneration: Neural Organoid Transplantation in the CNS.Cell proliferation · 2026Review
- Generation of a new immunodeficient rat model of retinal degeneration with LSL TdTomato reporter and TdTomato-Pcp2 expression.bioRxiv : the preprint server for biology · 2026Article
- Animal models for the evaluation of retinal stem cell therapies.Progress in retinal and eye research · 2025Review
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
backgroundPhotoreceptor (PR) enriched retinal organoid (RO) sheets (human embryonic stem cell [hESC]-derived ROs) resulted in restoration of visual acuity in immunocompromised retinal degenerate (RD) animal models after transplantation. Further assessment of their clinical potential requires evaluation in immunocompetent RD disease models with effective immune suppression. We characterized safety and efficacy profiles of both donor tissues and prospective immunosuppressive treatments in vitro; and in vivo in immunocompetent RD rats (strain SD-foxn1 Tg(S334ter)3Lav).
methodsRetinal identity of ROs was validated by histology, flow cytometry and gene expression profiling, and their immunogenicity to sensitized human immune cells was measured by mixed lymphocyte reactions (MLR). We measured the effect of RO exposure for 1-4 weeks to therapeutic concentrations of our immunosuppressant drugs of choice on gene expression and metabolic function using quantitative PCR (qPCR) and functional and structural fluorescence lifetime imaging (FLIM), respectively. Immunocompetent RD graft recipients were immunosuppressed by implanted tacrolimus (TAC) pellets and mycophenolate mofetil (MMF) in food. In vivo, LCMS aided assessments of drug pharmacodynamics. Flow cytometry immunophenotyping and assay of post-surgery cytokines were used to assess and monitor drug efficacy. Retinal transplants were imaged in situ using optical coherence tomography (OCT) at defined time points post-surgery. Visual function was assessed by optokinetic tests (OKT) and superior colliculus electrophysiology recording. At study endpoints, immune cell infiltration and donor photoreceptor engraftment into host retinal architecture was evaluated by immunohistochemistry.
resultsImmunosuppressive drugs have no negative effects on RO development and metabolism in vitro; and low alloreactivity of ROs determined by MLR may be predictive to that of human graft recipients. In vivo, minimum effective dosing ranges of TAC and MMF were determined. We characterized the mechanisms and critical immune populations implicated in rejection; and subsequently demonstrated their effective suppression in our xenograft RD model. OKT measured significant visual improvement after RO transplantation. Transplants developed most retinal cell types including photoreceptors; and integrated with the host retina. However, immunosuppression induced higher sensitivity to ketamine anesthesia.
conclusionsThis study proves the concept that immunosuppression is likely tolerable in retinal transplantation and human stem cell therapy for retinal degeneration patients.
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