Evidence map›Paper›PMID 40230358›Full record

ArticleRegenerative therapy2025

Human corneal organoid has a limbal function that supplies epithelium to the cornea with limbal deficiency.

Kazunari Higa, Mifuyu Ishiwata, Reona Kimoto, Masatoshi Hirayama, Takefumi Yamaguchi, Shigeto Shimmura

Abstract read
In one paragraph

Article in Regenerative therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

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0cells of the map it votes in
2citing papers in PubMed
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1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Kazunari HigaCornea Center Eye Bank, Tokyo Dental College Ichikawa General Hospital, 5-11-13 Sugano, Ichikawa, Chiba, 272-8513, Japan.
Mifuyu IshiwataCornea Center Eye Bank, Tokyo Dental College Ichikawa General Hospital, 5-11-13 Sugano, Ichikawa, Chiba, 272-8513, Japan.
Reona KimotoCornea Center Eye Bank, Tokyo Dental College Ichikawa General Hospital, 5-11-13 Sugano, Ichikawa, Chiba, 272-8513, Japan.
Masatoshi HirayamaDepartment of Ophthalmology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
Takefumi YamaguchiCornea Center Eye Bank, Tokyo Dental College Ichikawa General Hospital, 5-11-13 Sugano, Ichikawa, Chiba, 272-8513, Japan.
Shigeto ShimmuraDepartment of Ophthalmology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Introduction: Patients with limbal dysfunction, which occurs when corneal epithelial stem cells are depleted, require the transplantation of donor corneal epithelial stem cells or donor-independent cell sources. This study aimed to establish organoids with limbal epithelial progenitor cell function from the central cornea, where stem cells do not reside Methods: After treatment with collagenase, central corneal epithelial cells were scraped from corneal tissue and seeded onto Matrigel. For comparison, cells were collected from the limbus. The cells were cultured in Limbal Phenotype Maintenance Medium (LPMM). After 1 month, the organoids were observed in terms of number and size, immunohistochemistry, cell cycle, and colony-forming efficiency. Organoids were also transplanted into a rabbit model of limbal deficiency. Results: Although we were able to form organoids from the central cornea, the number of organoids from the cornea was small (approximately one tenth compared to the limbus) after 1-month culture. Cornea-derived organoids were similar in shape and size to limbal-derived organoids, and expressed keratin 15 and p63, which are characteristics of the limbal epithelium, as well as collagen type IV, laminin, and tenascin-C, which are limbal basement membrane components. Cornea-derived organoids also showed colony forming efficiency, slow-cycling cells, and label-retaining cells. Transplanted corneal organoids were observed in the limbus of a rabbit limbal deficiency model, and the presence of organoid-derived cells extending into the host cornea was confirmed by immunohistochemistry using anti-human nuclei, -K12, -collagen type IV, and -laminin antibodies. Conclusions: Our data suggest that corneal organoids de-differentiated to gain a limbal phenotype and functionally supplied corneal epithelium in a rabbit limbal deficiency model for up to 1 month.

Indexed as

Corneal epithelial progenitor cellsCorneal epithelial regenerationCorneal limbal functionLimbal deficiencyNicheOrganoid

Identifiers

PMID40230358
PMCPMC11995013

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