Mass Eye and Ear-led trial of procedure that took stem cells from a healthy eye and transplanted them into the damaged eye, safely restored corneal surfaces in 14 patients who were followed for 18 months.
A new stem cell therapy, CALEC, has demonstrated a 92% success rate in regenerating corneas and restoring vision. This breakthrough procedure is still experimental but shows immense promise for those with previously untreatable eye injuries.
An expanded clinical trial that tested a groundbreaking, experimental stem cell treatment for blinding cornea injuries found the treatment was feasible and safe in 14 patients who were treated and followed for 18 months, and there was a high proportion of complete or partial success. The results of this new phase 1/2 trial published March 4, 2025 in Nature Communications.
A recent clinical trial testing an experimental stem cell treatment for severe cornea injuries found the therapy to be both safe and effective. Fourteen patients received the treatment and were monitored for 18 months, with a high rate of complete or partial success. The findings from this phase 1/2 trial were published today (March 4, 2025) in Nature Communications.
How CALEC Works: A Revolutionary Process
The treatment, known as cultivated autologous limbal epithelial cells (CALEC), was developed at Mass Eye and Ear, part of the Mass General Brigham healthcare system. The process involves taking stem cells from a healthy eye through a small biopsy, growing them into a tissue graft over two to three weeks, and then surgically transplanting the graft onto the damaged cornea.
“Our first trial in four patients showed that CALEC was safe and the treatment was possible,” said principal investigator Ula Jurkunas, MD, associate director of the Cornea Service at Mass Eye and Ear and professor of Ophthalmology at Harvard Medical School. “Now we have this new data supporting that CALEC is more than 90% effective at restoring the cornea’s surface, which makes a meaningful difference in individuals with cornea damage that was considered untreatable.”
Principal investigator Ula Jurkunas, MD, performs the first stem cell transplantation of the CALEC clinical trial in 2018 at Mass Eye and Ear in Boston, on a patient who suffered a severe chemical burn in his eye. Credit: Mass Eye and Ear
Efficacy and Safety: Encouraging Outcomes
Researchersshowed 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 reached complete success by the study end visit. An additional analysis of CALEC’s impact on vision showed varying levels of improvement of visual acuity in all 14 CALEC patients.
CALEC displayed a high safety profile, with no serious events occurring in either the donor or recipient eyes. One adverse event, a bacterial infection, occurred in one participant, eight months after the transplant due to chronic contact lens use. Other adverse events were minor and resolved quickly following the procedures.
Human eye anatomy.
Future Steps: Expanding Research and Approval Pathway
CALEC remains an experimental procedure and is currently not offered at Mass Eye and Ear or any U.S. hospital, and additional studies will be needed before the treatment is submitted for federal approval.
The CALEC trial is the first human study of a stem cell therapy to be funded by the National Eye Institute (NEI), a part of the National Institutes of Health (NIH) and was the first stem cell therapy in the eye in the U.S. Other research collaborators include Jia Yin, MD, PhD and Reza Dana, MD at Mass Eye and Ear, Jerome Ritz, MD, of Dana-Farber Cancer Institute’s Connell and O’Reilly Families Cell Manipulation Core Facility, where the manufacturing of the stem cell graft takes place; and Myriam Armant, PhD, of Boston Children’s Hospital; and the JAEB Center for Health Research.
The Science Behind Cornea Regeneration
The cornea is the clear, outermost layer of the eye. Its outer border, the limbus, contains a large volume of healthy stem cells called limbal epithelial cells, which maintain the eye’s smooth surface. When a person suffers a cornea injury, such as a chemical burn, infection or other trauma, it can deplete the limbal epithelial cells, which can never regenerate. The resulting limbal stem cell deficiency renders the eye with a permanently damaged surface where it can’t undergo a corneal transplant, the current standard of care for vision rehabilitation. People with these injuries often experience persistent pain and visual difficulties.
CALEC trial principal investigator Ula Jurkunas, MD, associate director of the Cornea Service at Mass Eye and Ear and professor of Ophthalmology at Harvard Medical School, in her lab at Mass Eye and Ear in Boston. Credit: Mass Eye and Ear
Two Decades of Research Lead to a Breakthrough
This need led Jurkunas as a junior scientist and Dana, director of the Cornea Service at Mass Eye and Ear, to explore a new approach for regenerating limbal epithelial cells. Nearly two decades later, following preclinical studies and collaborations with researchers at Dana-Farber and Boston Children’s, it was possible to consistently manufacture CALEC grafts that met stringent quality criteria needed for human transplantation. The clinical trial was approved by the U.S. Food and Drug Administration (FDA) and Mass General Brigham Institutional Review Board (IRB) and the first patient was treated in 2018 at Mass Eye and Ear. Successful completion of the trial was accomplished through close coordination between Jurkunas’ surgical team and the cell manufacturing facility at Dana-Farber.
Studies like this show the promise of cell therapy for treating incurable conditions. Mass General Brigham’s Gene and Cell Therapy Institute is helping to translate scientific discoveries made by researchers into first-in-human clinical trials and, ultimately, life-changing treatments for patients.
Expanding Treatment Options: The Future of CALEC
As an autologous therapy, one limitation of this approach is that it is necessary for the patient to have only one involved eye so a biopsy can be performed to get starting material from the unaffected normal eye.
“Our future hope is to set up an allogeneic manufacturing process starting with limbal stem cells from a normal cadaveric donor eye,” said Dr. Ritz. “This will hopefully expand the use of this approach and make it possible to treat patients who have damage to both eyes.”
In the interim, future CALEC studies should include larger numbers of patients at multiple centers, with longer follow-ups and a randomized-control design.
Towards FDA Approval: The Next Frontier
“We feel this research warrants additional trials that can help lead towards FDA approval,” said Jurkunas. “While we are proud to have been able to bring a new treatment from the lab bench to clinical trials, our guiding objective was and always will be for patients around the country to have access to this effective treatment.”
Reference: “Cultivated autologous limbal epithelial cell (CALEC) transplantation for limbal tem cell deficiency: a phase I/II clinical trial of the first xenobiotic-free, serum-free, antibiotic-free manufacturing protocol developed in the US” by Ula V. Jurkunas, Aaron R. Kaufman, Jia Yin, Allison Ayala, Maureen Maguire, Lassana Samarakoon, Lynette K. Johns, Mohit Parekh, Sanming Li, Alex Gauthier, Helene Negre, Kit L. Shaw, Diego E. Hernandez Rodriguez, Heather Daley, Reza Dana, Myriam Armant and Jerome Ritz, 4 March 2025, Nature Communications.
DOI: 10.1038/s41467-025-56461-1
In addition to Jurkunas, Ritz and Armant, co-authors of the study include Aaron R. Kaufman (MEE), Jia Yin (MEE), Allison Ayala (Jaeb), Maureen Maguire (Jaeb), Lassana Samarakoon (Jaeb), Lynette K. Johns (MEE), Mohit Parekh (MEE), Sanming Li (MEE), Alex Gauthier (MEE), Helene Negre (DFCI), Kit L. Shaw (DFCI), Diego E. Hernandez Rodriguez (DFCI), Heather Daley (DFCI), and Reza Dana (MEE).
This research is funded by National Eye Institute (NEI) of the National Institutes of Health (NIH) under Award Numbers UG1EY026508, UG1EY027726, and UG1EY027725. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
Disclosures: CALEC is patent pending. Jurkunas and Dana have financial interest in OcuCell, Inc., a company developing living ophthalmic cell-based therapies for treating eye disease. Armant serves on the scientific advisory board for OcuCell, Inc. Ritz receives research funding from Kite/Gilead, Novartis and Oncternal and serves on Scientific Advisory Boards for Astraveus, Garuda Therapeutics, Smart Immune, Tolerance Bio, and TriArm Therapeutics. The remaining authors declare no competing interests.
