In early November, researchers at Osaka University in Japan published groundbreaking findings in the scientific journal The Lancet, introducing the world's first stem cell treatment that successfully restores vision in patients with limbal stem-cell deficiency (LSCD). The team, led by Professor Koji Nishida, used induced pluripotent stem cells (iPS) to perform corneal transplants, marking a significant advancement in treatment.
Limbal stem-cell deficiency is a rare disease affecting the eye that can lead to blindness. It occurs when stem cells in the cornea cannot regenerate and repair the surface, leading to the formation of scar tissue and progressive vision loss. According to experts, LSCD is characterized by the loss or deficiency of stem cells in the limbus, which are vital for the regeneration of the corneal epithelium and the barrier function of the limbus. Symptoms of LSCD include pain, painful light sensitivity, inflammation, and excessive ingrowth of blood vessels. The limbal stem cells normally maintain the outermost layer of the cornea, and their depletion leads to significant visual impairment.
Current treatment options for LSCD are limited and typically involve risky corneal transplants from deceased donors or invasive procedures using stem cells from the patient's own healthy eye, which have uncertain outcomes and a high risk of rejection. These treatment options present risks of immune rejection, infections, glaucoma, and injury to the structures in the eye. When both eyes are affected, corneal transplants from deceased donors are an option, but they are sometimes rejected by the recipient's immune system. Previous attempts to restore vision in patients with LSCD faced many challenges, including severe side effects.
In the new approach, the Osaka University researchers utilized induced pluripotent stem cells, which are created by artificially reprogramming blood cells from healthy donors to an embryonic-like state, to perform corneal transplants. The scientists extracted blood cells from healthy donors and reprogrammed them into an embryonic-like state. These cells were then transformed into a thin, transparent sheet of cobblestone-shaped corneal epithelial cells. During the surgical procedure, the researchers scraped off the layer of scar tissue covering the damaged cornea in one eye of each recipient. The reprogrammed cells were placed onto the damaged cornea and protected by a soft contact lens after the procedure.
The study involved four participants—two women and two men aged 39 to 72—suffering from LSCD in both eyes. All four participants showed an immediate improvement in eyesight following the transplants. Three participants with severe vision impairment experienced significant and lasting improvements in their vision for over a year. The vision improvements persisted in all but one recipient, who showed slight deteriorations during a one-year observation period. One participant experienced a slight reversal of vision improvement over the course of a year. Two years after receiving the transplants, none of the recipients experienced serious side effects, and the grafts did not show clear signs of being attacked by the recipients' immune systems, even in two patients who did not receive immunosuppressive drugs.
Kapil Bharti, a stem cell researcher at the U.S. National Eye Institute in Bethesda, described the results as "impressive" and stated: "This is an exciting development." Bharti emphasized: "It's important and a relief to see that the grafts were not rejected. But more transplants are needed to be certain of the safety of the procedure." Jeanne Loring, a stem cell researcher at the Scripps Research Institute in La Jolla, California, stated: "The results justify treating more patients," indicating that experimentation with this method will continue.
The improvement in vision could be due to the proliferation of the transplanted cells in the cornea or the removal of scar tissue before the transplantation. It is still unclear to the scientists what the improvement in eyesight is due to. The return of eyesight could also be due to the transplant stimulating the recipient's own cells to migrate from other areas of the eye and renew the cornea. It is likely that the transplanted cells themselves multiplied in the recipients' corneas.
The Osaka University researchers are currently focusing on testing the safety and durability of new stem cell applications, including the use of induced pluripotent stem cells, which have shown promise in treating eye diseases. Kohji Nishida's team will begin clinical trials in March 2025 to better evaluate the efficacy of the treatment, which is apparently safe but needs to be tested in larger trials. The next steps for the researchers include conducting larger trials with the cell sheets to gain a greater understanding of patient response.
Cornea-related blindness affects approximately 10 million people worldwide, a significant number of whom are children. The use of stem cells in healthcare is increasing exponentially in recent years. In 2023, stem cells were responsible for treating diabetes in a clinical study conducted in China. Although there may be many gaps in stem cell research and practice, clinical studies can help build the future of new treatments one study at a time.
Sources: 20 Minutos, Sat.1, Youm7 (Entertainment), WIRED Middle East
This article was written in collaboration with generative AI company Alchemiq