Stem cell shots: Unveiling a safer way to treat inflammatory eye diseases

Graft-versus-host disease (GVHD) is a common and severe complication that occurs after stem cell transplantation, where the donor’s immune cells attack the recipient’s tissues. Ocular manifestation of GVHD is among the most challenging to treat, often leading to chronic inflammation and corneal tissue damage, which can result in loss of vision. Conventional treatments, including corticosteroids, are frequently used to manage ocular inflammation associated with GVHD. However, these therapies come with significant side effects, including the risk of glaucoma and other ocular complications.

Mesenchymal stromal cells (MSCs), a heterogeneous population of cells present in various tissues of the body, are known to possess immunoregulatory and modulatory properties. Their ability to navigate to sites that have suffered injury and inflammation in the body makes them highly sought after for the development of regenerative treatments and pharmaceuticals. In fact, several studies have explored the potential of human-derived MSCs for treating such conditions. However, much remains to be known about their true potential for the treatment of ocular GVHD and advancing their clinical application.

Now, in a new study conducted by Dr. Shigeto Shimmura and Robert M. Rusch from Fujita Health University and Keio University, Japan, researchers have proposed a novel therapy for ocular GVHD involving MSCs. The team explored the potential of regenerative mesenchymal stem cells in reducing ocular inflammation in GVHD-infected mice. Their study, published in The Ocular Surface, explores the potential of adipose-derived MSCs (adMSCs) to reduce inflammation and promote tissue repair​. It was made available online on November 13, 2024, and published in Volume 34 of the journal in October 2024.

Elaborating on the rationale behind this study, Dr. Shimmura says, “adMSCs are easy to obtain and have demonstrated benefits in corneal tissue regeneration. Moreover, we injected adMSCs after the onset of GVHD and also monitored them over an extended period of time, helping us verify their therapeutic applicability.”

Using mice that had been induced with chronic GVHD, researchers administered adMSCs into the eyes via a single injection. Over three weeks, the researchers found that the adMSC treatment increased regulatory T cells while reducing inflammation in the mice. Further, adMSC-conditioned media enhanced cell migration and proliferation in laboratory scratch tests, showcasing the regenerative capacity of the cells. Importantly, the injected cells disappeared within a week, minimizing the risk of long-term complications such as tumor formation.

“Our findings highlight the dual benefits of adMSCs: They suppress inflammation and enhance tissue healing,” elaborates Dr. Shimmura, senior author and researcher. Adding further, he says, “This makes them a promising candidate for treating immune-related ocular disorders without systemic side effects.”

These observations point to the potential of adMSCs as a targeted, localized therapy for immune-related eye conditions. Unlike systemic treatments, these local injections ensured the therapeutic effects remained localized to the ocular surface. “Our work underscores the safety and efficacy of adMSCs, paving the way for clinical trials in humans,” notes Dr. Shimmura.

With their immunoregulatory and regenerative properties, adMSCs may offer a lifeline to patients suffering from chronic ocular GVHD and related inflammatory diseases. Future studies, however, need to focus on dose optimization and delivery methods to maximize therapeutic outcomes.

In summary, these results offer hope for a future where innovative, stem cell-based therapies can transform the way we manage autoimmune diseases, offering patients better outcomes and improved quality of life.

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Reference
DOI: 10.1016/j.jtos.2024.11.001

About Fujita Health University
Fujita Health University is a private university situated in Toyoake, Aichi, Japan. It was founded in 1964 and houses one of the largest teaching university hospitals in Japan in terms of the number of beds. With over 900 faculty members, the university is committed to providing various academic opportunities to students internationally. Fujita Health University has been ranked eighth among all universities and second among all private universities in Japan in the 2020 Times Higher Education (THE) World University Rankings. THE University Impact Rankings 2019 visualized university initiatives for sustainable development goals (SDGs). For the “good health and well-being” SDG, Fujita Health University was ranked second among all universities and number one among private universities in Japan. The university became the first Japanese university to host the "THE Asia Universities Summit" in June 2021. The university’s founding philosophy is “Our creativity for the people (DOKUSOU-ICHIRI),” which reflects the belief that, as with the university’s alumni and alumnae, current students also unlock their future by leveraging their creativity.
Website: https://www.fujita-hu.ac.jp/en/index.html

About Professor Shigeto Shimmura from Fujita Health University
Shigeto Shimmura, MD, Ph.D., is a leading researcher in regenerative medicine and ophthalmology at Fujita Health University, Japan. His work focuses on innovative cell-based therapies for ocular diseases. With a strong background in immunology and stem cell biology, Dr. Shimmura has made significant contributions to understanding immune modulation and regenerative mechanisms in eye disorders, including graft-versus-host disease. He has 312 publications and 14,362 citations to his name.

Funding information
The study was supported by a grant from the Japan Society for the Promotion of Science (JSPS) (KAKENHI Grant #22H03245). The study was funded in part by Rohto Pharmaceuticals.