In Brief | Ophthalmology | Stem Cell Therapy
Stem cell breakthrough: iPSC-Derived corneal transplants show promise in treating vision loss from Limbal Stem Cell Deficiency
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Time to listen: 06:39
Published on MedED: 19 November 2024
Originally Published: 16 November 2024
Sourced: The Lancet
Type of article: In Brief
MedED Catalogue Reference: MOIB004
Category: Ophthalmology
Cross Reference: Corneal Conditions, Stem Cell Therapy
Keywords: corneal transplant, stem cell, limbal stem-cell deficiency
Originally Published: 16 November 2024
Sourced: The Lancet
Type of article: In Brief
MedED Catalogue Reference: MOIB004
Category: Ophthalmology
Cross Reference: Corneal Conditions, Stem Cell Therapy
Keywords: corneal transplant, stem cell, limbal stem-cell deficiency
Key Takeaway
Top
Human iPSC-derived corneal epithelial cell sheets (iCEPS) show promise as a novel regenerative therapy for limbal stem cell deficiency (LSCD), demonstrating significant improvements in corneal health and visual acuity without immunological rejection
Originally published in The Lancet,16 November 2024. This summary does not represent the original research, nor is it intended to replace the original research. Content Disclaimer
The corneal limbus— the junction between the cornea, conjunctiva, and sclera—is vital for maintaining corneal health and supporting the entire visual system.
This highly vascularised, innervated, and pigmented region contains specialised niches that house various stem cell types, including those responsible for corneal epithelium, stromal keratocytes, corneal endothelium, and trabecular meshwork.1
When these stem cells are absent or insufficient in number, a condition known as limbal stem cell deficiency (LSCD) occurs, which causes conjunctival tissue overgrowth, scarring, and vision loss.
LSCD can be unilateral (due to trauma) or bilateral (from immune-mediated diseases or hereditary conditions). Current treatments include ocular surface optimization and corneal epithelial grafting, but these have limitations, such as variable outcomes and the risk of rejection.
This ground-breaking clinical study at Osaka University Hospital explored a new regenerative therapy using human induced pluripotent stem cells (iPSCs) to treat LSCD.
Editors Note
Pluripotent stem cells, such as human induced pluripotent stem cells, are considered "master" cells. They have unlimited self-renewal capacity and exhibit rapid growth under optimal in vitro conditions.2
To obtain their grafts, the researchers employed a self-formed ectodermal autonomous multizone cultivation protocol - SEAM - that mimics eye development, generating precursor cells for ocular tissues.
This technique allowed the creation of iPSC-derived corneal epithelial cell sheets (iCEPSs), which had been previously shown to reconstruct the cornea in animal models.
Four patients with LSCD were enrolled in this study.
The first pair of patients consisted of a 44-year-old female with idiopathic LSCD and a 66-year-old male with ocular mucous membrane pemphigoid. (Referred to here onwards as patients 1 -and 2)
The second pair included a 72-year-old male with idiopathic LSCD and a 39-year-old female with toxic epidermal necrosis. (Referred to here onwards as patients 3 and 4)
Patients 1 and 2 received low-dose cyclosporin, while patients 3 and 4 did not require immunosuppressive therapy or human leukocyte antigen (HLA) matching.
During surgery, a single iCEPS was sutured onto the corneal surface and then protected with a therapeutic contact lens.
Postoperative care included antibiotics, corticosteroids, and mycophenolic acid (for patient 2’s primary disease). The study’s primary outcome was safety, while secondary measures assessed LSCD stage, corneal health, visual acuity, and quality of life over 52 weeks.
The following findings were recorded:
Primary Outcomes
No serious adverse events, immunological rejection, or tumour formation were observed.
Minor non-serious adverse events occurred but were manageable, indicating a good safety profile for the iCEPS transplant.
Secondary Outcomes
All patients demonstrated clinical improvements in LSCD symptoms. Specifically:
LSCD severity decreased from stage III to IA in patients 1 and 2, and from IIB to IA in patient 3, with sustained recovery during follow-up.
Patient 4 showed improvement to stage IA at 32 weeks but regressed to stage IIB by the 1-year mark.
Corneal epithelial defects improved, with patients 1, 2, and 3 maintaining a grade 0 defect at 52 weeks, while patient 4 remained at grade 1. S
Visual acuity gains were significant:
Corrected decimal distance visual acuity improved by 10.0, 11.8, 6.6, and 2.8 logMAR lines in patients 1, 2, 3, and 4, respectively.
Corneal opacification reduced across all patients, while neovascularization decreased in patients 1 and 2 but remained unchanged or worsened in patients 3 and 4.
Symblepharon severity was stable for all participants at the 52-week mark.
Subjective symptoms either improved or stabilized in all cases.
Quality of life (QOL) scores at 52 weeks improved for patients 1, 2, and 3 but declined for patient 4.
In conclusion, the iCEPS transplantation showed promising results in treating LSCD, with significant improvements in clinical manifestations, visual acuity, and corneal health, especially in patients with less severe conditions.
The procedure was safe, with no signs of rejection or severe adverse effects. Despite the variability in response, particularly in patients with advanced disease, the overall positive outcomes suggest iCEPS as a potential regenerative therapy for LSCD.
A larger clinical trial is planned to confirm these findings and further assess the therapy’s efficacy.
This study was registered on UMIN, UMIN000036539
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