ArticleThe Journal of clinical investigation2022
Long-term corneal recovery by simultaneous delivery of hPSC-derived corneal endothelial precursors and nicotinamide.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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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
18 citing papers in PubMed, 67 citations in OpenAlex.
- Metabolic and redox adaptations of the corneal endothelium: From metabolic plasticity to therapeutic opportunities.Redox biology · 2026Review
- Role of stem cells in ocular diseases: Progress and challenges.Journal of biomedical research · 2026Article
- Recent advances in corneal specular microscopy image analysis through artificial intelligence.PLOS digital health · 2026Review
- Strategies for Differentiation of Corneal Endothelial Cells From Stem Cells: Current Advances and Challenges.Stem cells international · 2026Review
- A simple and standardized method supports efficient derivation of clinical-grade human embryonic stem cells under feeder- and xeno-free conditions.Stem cell research & therapy · 2025Article
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- Clinical Applications of Corneal Cells Derived from Induced Pluripotent Stem Cells.Biomolecules · 2025Review
- Artificial Cornea Substitute Based on Hydrogel Skeletons with Natural Stromal Hierarchical Structure and Extracellular Matrix for Sutureless Transplantation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Matrix glycosaminoglycans and proteoglycans in human cornea organoids and similarities with fetal corneal stages.The ocular surface · 2025Article
- RAD21 deficiency drives corneal to scleral differentiation fate switching via upregulating WNT9B.iScience · 2024Article
- Status and prospects for the development of regenerative therapies for corneal and ocular diseases.Regenerative therapy · 2024Review
- Safety and efficacy of human ESC-derived corneal endothelial cells for corneal endothelial dysfunction.Cell & bioscience · 2023Article
- The Innovative Biomaterials and Technologies for Developing Corneal Endothelium Tissue Engineering Scaffolds: A Review and Prospect.Bioengineering (Basel, Switzerland) · 2023Review
- Single-cell RNA sequencing reveals new subtypes of lens superficial tissue in humans.Cell proliferation · 2023Article
- Ex vivo cultivated retinal pigment epithelial cell transplantation for the treatment of rabbit corneal endothelial dysfunction.Eye and vision (London, England) · 2023Article
- Article
- iPSC-Derived Corneal Endothelial Cells.Handbook of experimental pharmacology · 2023Article
- Corneal Endothelial Characteristics in Normal Chinese Han Children and Youngsters: A Study from the Specular Microscopy Descriptions.Disease markers · 2022Article
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human pluripotent stem cells (hPSCs) hold great promise for the treatment of various human diseases. However, their therapeutic benefits and mechanisms for treating corneal endothelial dysfunction remain undefined. Here, we developed a therapeutic regimen consisting of the combination of hPSC-derived corneal endothelial precursors (CEPs) with nicotinamide (NAM) for effective treatment of corneal endothelial dysfunction. In rabbit and nonhuman primate models, intracameral injection of CEPs and NAM achieved long-term recovery of corneal clarity and thickness, similar with the therapeutic outcome of cultured human corneal endothelial cells (CECs). The transplanted human CEPs exhibited structural and functional integration with host resident CECs. However, the long-term recovery relied on the stimulation of endogenous endothelial regeneration in rabbits, but predominantly on the replacing function of transplanted cells during the 3-year follow-up in nonhuman primates, which resemble human corneal endothelium with limited regenerative capacity. Mechanistically, NAM ensured in vivo proper maturation of transplanted CEPs into functional CECs by preventing premature senescence and endothelial-mesenchymal transition within the TGF-β-enriched aqueous humor. Together, we provide compelling experimental evidence and mechanistic insights of simultaneous delivery of CEPs and NAM as a potential approach for treating corneal endothelial dysfunction.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.