Stem Cell Transplant Restores Vision After Blinding Eye Injuries

 

• Transplanted autologous corneal stem cells successfully repaired corneal injuries in patients.
• Over 90% of patients achieved complete or partial success.
• The procedure proved safe with no serious adverse events reported.

Transplanted epithelial stem cells from a healthy eye repaired irreversible corneal injury and restored at least partial vision in more than 90% of patients, a preliminary clinical study showed.

Within 3 months of the transplant, seven of 14 patients had completely restored corneas, increasing to 11 of 14 at 12 months. Including partial responses, more than 90% of the patients achieved successful outcomes at 12 and 18 months.

The transplant procedure proved to be safe, with no serious systemic adverse events, particularly serious infections, despite no use of antibiotics, reported Ula V. Jurkunas, MD, of Mass Eye and Ear and Harvard Medical School in Boston, and co-authors in Nature Communicationsopens in a new tab or window.

The results met or exceeded expectations, she told MedPage Today.

"We had some literature on similar technologies used in Europe and Asia, and those treatments were maybe 70-80% successful," said Jurkunas. "Our study, although it's not a large study, was 92% successful at 18 months, so we felt very good about the protocol and the process of our products and our stem cells. We felt like it was kind of above expectations."

The initial study was limited to patients with unilateral limbal stem cell deficiency (LSCD) caused by chemical burns and other serious eye injuries. Healthy stem cells were harvested from a patient's healthy eye, processed, and transplanted into the injured eye. Whether allogeneic transplants are feasible for patients with bilateral LSCD, caused by injuries or inherited eye diseases, remains unknown but represents the "holy grail" of limbal stem cell transplantation research.

"For those patients [with bilateral LSCD] we can develop a similar protocol and use cadaveric corneal stem cells and grow them in the lab," said Jurkunas. "That is a next step. We don't have a trial on that, and we cannot offer that to patients yet. But that is what we will be doing next, for bilateral cases, taking allogeneic limbal stem cells."

The preliminary results are very promising for a treatment that could potentially address a significant unmet clinical need, said Christopher Starr, MD, of Weill Cornell Medicine in New York City.

"This is a small preliminary phase I/II study largely looking at safety and feasibility and was not masked, randomized, or controlled," Starr, who is also an American Academy of Ophthalmology spokesperson, told MedPage Today. "That being said, the primary safety and feasibility outcomes were achieved and the secondary outcomes of complete and partial success rates were also quite impressive and highly encouraging."

A challenging aspect of the procedure is the need for sufficient stem cells in a patient's healthy eye to permit safe harvesting and cultivation of the cellular construct without jeopardizing the health of the better eye, he added.

"Perhaps in the future, as the manufacturing process improves, these large autologous stem cell grafts can be created with only a few healthy and viable stem cells," said Starr.

Corneal clarity depends on the regenerative capacity of corneal limbal epithelial stem cells, which provide specialized corneal epithelium and serve as a barrier between conjunctiva and cornea, Jurkunas and co-authors noted in their background information. LSCD is characterized by "conjunctivalization" of the corneal surface and diminished integrity of the corneal epithelium. Neovascularization, inflammation, scarring, and opacity may occur, leading to decreased vision and debilitating symptoms.

In patients with unilateral LSCD, donor cells from a patient's healthy eye can be harvested and transferred to the injured eye in an effort to stimulate regeneration of limbal stem cells. Strategies to treat LSCD include direct grafting of autologous tissue, simple limbal epithelial transplantation (SLET), and cultivated limbal epithelial transplantation (CLET). Although SLET requires less donor tissue, limbal epithelial stem cells are not expanded before grafting, and clinical experience to date has limited long-term follow-up, the authors noted.

The clinical trial began in 2016, and Jurkunas and colleagues previously reportedopens in a new tab or window for the first four patients treated with their version of CLET, called cultivated autologous limbal epithelial cells (CALEC). The updated report includes all 14 patients treated to date. Enrollment attracted patients from multiple states, not just those living in the Boston area, and follow-up has reached 18 months for all patients. The primary and secondary endpoints were safety and efficacy, respectively.

A single bacterial infection occurred, related to chronic contact lens use; investigators observed no other primary safety events.

Complete success was defined as improvement in corneal surface integrity (decrease in epithelial defect or decrease in corneal surface staining if no defect at baseline). The proportion of patients achieving complete success increased from 50% at 3 months to 79% and 77% at 12 and 18 months, respectively. An additional two patients achieved partial success by 18 months, defined as a decrease in neovascularization or symptomatology, bringing the overall success rate to 92%.

Transplantation was unsuccessful in one case, and another patient underwent a second CALEC procedure before 18 months.

"Three of our patients actually will have repeat procedures because we felt like one dose of stem cells was just not enough," said Jurkunas. "So, it's repeatable, and that's another good part about [CALEC]."

Though the initial patient cohort included only adults, the procedure likely can be performed in children, she continued. The study also suggests that earlier treatment might lead to better results. Some of the participants' eye injuries occurred many years ago, and their injured corneas had more extensive scarring and fibrosis. Outcomes in those patients tended to be less favorable.

Disclosures

The study was supported by the National Eye Institute.

Jurkunas disclosed a relationship with OcuCell Inc and has a patent pending. Some co-authors also disclosed a relationship with OcuCell, as well as Kite/Gilead, Novartis, Oncternal, Astraveus, Garuda Therapeutics, LifeVault Bio, Smart Immune, Tolerance Bio, and TriArm Therapeutics.

Starr disclosed relationships with Bausch & Lomb, TearLab, AbbVie, Sight Sciences, RxSight, Beaver Visitec, and BioTissue Holdings.

Primary Source

Nature Communications

Source Reference: opens in a new tab or windowJurkunas UV, 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 U.S." Nat Commun 2025; DOI: 10.1038/s41467-025-56461-1.

https://www.medpagetoday.com/ophthalmology/generalophthalmology/114480