Molecular characterization and sub-retinal transplantation of hypoimmunogenic human retinal sheets in a minipig model of severe photoreceptor degeneration
Bibliographic record
Abstract
Retinal degenerative diseases affect millions of people worldwide, and legal blindness is generally associated with the loss of cone photoreceptors located in the central region of the retina called the macula. Currently, there is no treatment to replace the macula. Addressing this unmet need, we employed control isogenic and hypoimmunogenic induced pluripotent stem cell lines to generate spontaneously polarized retinal sheets (RSs). RSs were enriched in retinal progenitor and cone precursor cells, which could differentiate into mature S- and M/L-cones in long-term cultures. Single-cell RNA-seq analysis showed that RSs recapitulate the ontogeny of the developing human retina. Isolation of neural rosettes for sub-retinal transplantation effectively eliminated unwanted cells such as RPE cells. In a porcine model of chemically induced retinal degeneration, grafts integrated the host retina and formed a new, yet immature, photoreceptor layer. In one transplanted animal, functional and immunohistochemical assays suggest that grafts exhibited responsiveness to light stimuli and established putative synaptic connections with host bipolar neurons. This study underscores the potential and challenges of RSs for clinical applications.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".