Novel stem cell therapy restores corneal damage previously believed irreversible
The authors said their results provide strong support that cultivated autologous limbal epithelial cell transplantation is safe and feasible
Investigators hope to move the experimental treatment into a Phase 3 study. Image credit: ©Enis – stock.adobe.com
A study led by researchers at the Massachusetts Eye and Ear, Boston, demonstrated that a novel stem cell therapy showed over 90% partial and complete success rates in repairing the corneal surfaces that had corneal damage believed to be irreversible,1 according to Ula Jurkunas, MD, PhD, who is associate director of the Cornea Service at the Mass Eye and Ear and professor of Ophthalmology at Harvard Medical School, Boston. The therapy, referred to as cultivated autologous limbal epithelial cells (CALEC) transplantation, was tested in a phase 1/2 clinical trial (Clinicaltrials.gov registration: NCT02592330).
The research team published their findings in Nature Communications.
They explained that the clarity of the cornea depends on the regenerative capacity of the limbal epithelial stem cells,2 which reside in the corneal limbus and continually provide specialised corneal epithelium while serving as a barrier between the conjunctiva and cornea.3 Limbal stem cell deficiency (LSCD) is characterised by conjunctivalisation of the corneal surface and other signs of diminished integrity of the corneal epithelium, such as neovascularisation, inflammation, scarring and opacity, which lead to decreased vision and debilitating symptoms (pain, photophobia and tearing).4 LSCD management aims to re-establish a healthy ocular surface and adjacent limbal niche to support limbal epithelial stem cells.5,6
CALEC procedure
The CALEC procedure, developed at the Mass Eye and Ear, is the “first xenobiotic-free, serum-free, antibiotic-free protocol developed in the US,” according to the investigators.
Dr Jurkunas and colleagues developed a two-stage manufacturing process that uses CALECs to treat blindness resulting from unilateral LSCD. The CALECs were obtained from healthy eyes during a biopsy, and they then were expanded into a cellular tissue graft that then was surgically transplanted into eyes with damaged corneas.
This research was built on the results from an experimental stem cell treatment performed in 4 eyes that indicated that the treatment was safe and feasible, according to Dr Jurkunas.
The primary outcomes were the feasibility (i.e., meeting release criteria) and safety (i.e., no ocular infection, corneal perforation or graft detachment); the secondary outcome was to investigate the efficacy based on improvement in the corneal epithelial surface integrity (complete success) or improvement in corneal vascularisation and/or participant symptomatology as measured by the Ocular Surface Disease Index and the Symptom Assessment in Dry Eye (partial success) questionnaires.
CALEC results
In a press release issued by Massachusetts Eye and Ear, the results were as follows:
- CALEC completely restored the cornea in 50% of participants at their 3-month visit and that rate of complete success increased to 79% and 77% at their 12- and 18-month visits, respectively.
- With two participants meeting the definition of partial success at 12 and 18 months, the overall success of CALEC was 93% and 92% at 12 and 18 months. Three participants received a second CALEC transplant, one of whom achieved complete success by the last study visit. An additional analysis of CALEC’s impact on vision showed varying levels of improvement of visual acuity in all 14 patients who underwent the procedure.
- CALEC displayed a high safety profile, with no serious events occurring in either the donor or recipient eyes. A bacterial infection occurred in one participant 8 months after the transplant due to chronic contact lens use. Other adverse events were minor and resolved quickly following the procedures.
In commenting on their findings, the authors said, “Our results provide strong support that CALEC transplantation is safe and feasible and further studies are needed to evaluate the therapeutic efficacy. The results of this trial will serve as a stepping-stone for establishing cellular therapy products as viable options for patients with LSCD.”
The goal is to move on to a phase 3 study.
CALEC is still an experimental procedure and is not offered at Mass Eye and Ear or any hospital in the US or elsewhere. Additional studies will be needed before the treatment is submitted for federal approval. The study was funded entirely by the NIH, the first human stem cell therapy trial to be funded by the NEI. The CALEC patent is pending. Dr Jurkunas and Reza Dana, a coauthor from the Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, have financial interests in OcuCell, Inc.
References
1. Jurkunas U, Kaufman AR, Yin J, et al. Cultivated autologous limbal epithelial cell (CALEC) transplantation for limbal stem cell deficiency: a phase I/II clinical trial of the first xenobiotic-free, serum-free, antibiotic-free manufacturing protocol developed in the US. Nat Comm. doi: 10.1038/s41467-025-56461-1
2. Tseng SC. Concept and application of limbal stem cells. Eye (Lond). 1989;3:141–157.
3. Townsend WM. The limbal palisades of Vogt. Trans Am Ophthalmol Soc. 1991;89:721–756.
4. Deng SX, Borderie V, Chan CC, et al. Global consensus on definition, classification, diagnosis, and staging of limbal stem cell deficiency. Cornea. 2019;38:364–375.
5. Deng SX, Kruse F, Gomes JAP, et al. Global consensus on the management of limbal stem cell deficiency. Cornea. 2020;39:1291–1302.
6. Masood F, Chang J-H, Akbar A, et al. Therapeutic strategies for restoring perturbed corneal epithelial homeostasis in limbal stem cell deficiency: current trends and future directions. Cells. 2022;11:3247. doi: 10.3390/cells11203247
Ula Jurkunas, MD, PhD | E: Ula_Jurkunas@meei.harvard.edu
Dr Jurkunas is from the Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston. She has a financial interest in OcuCell, Inc.
