Salivary gland mini-organs grown from pluripotent stem cells offer potential path to treating severe dry mouth

Extreme dry mouth, caused by radiation used to treat cancer and by autoimmune diseases such as Sjögren's disease, radically affects quality of life for sufferers. It can hamper speaking, swallowing and eating, and for years has seemed an intractable problem.

Attempts to stimulate the salivary glands to produce more saliva or to create artificial saliva have been ineffective.

Creating salivary glands from stem cells

Now, a small team of University at Buffalo researchers is working on a promising new strategy: creating salivary glands from human pluripotent stem cells (PSC) that could potentially be implanted into an individual's mouth.

"Human pluripotent stem cells can be derived from easily accessible adult somatic cells, such as skin or blood cells, making them an attractive cell source for therapeutic applications," says Stelios Andreadis, Ph.D., SUNY distinguished professor in the Department of Chemical and Biological Engineering in the School of Engineering and Applied Sciences at the University at Buffalo.

Andreadis is the co-principal investigator (PI) on the study that was published in Nature Communications. The co-PI is Olga Baker, Ph.D., D.D.S., a professor in the Department of Otolaryngology at the University of Missouri School of Medicine in Columbia.

Laura Sherwood, a Ph.D. candidate in biomedical engineering and a member of Andreadis' research group, was the first author on the paper, along with Ronel Samuel, who graduated with his Ph.D. in 2024. Last year, Sherwood earned an award for her research on this topic, which she presented at the 2025 Salivary Glands and Exocrine Biology Gordon Research Conference.

Following the steps of gland development

Andreadis explains that they are guiding these stem cells through steps that are similar to how salivary glands form during human development. They gradually produce salivary gland epithelial progenitor cells (SGEPs), which organize themselves into tiny, three-dimensional structures called organoids, or mini organs.

"Our findings suggest that salivary gland organoids may hold promise for studying salivary gland development, disease progression and drug screening, as well as for development of cell therapies for salivary gland regeneration," says Andreadis, who also serves as director of UB's Center of Cell, Gene and Tissue Engineering and is a member of the UB Center of Excellence in Bioinformatics and Life Sciences.

In 2012, Japanese stem cell researcher Shinya Yamanaka and the late British biologist John Gurdon were awarded the Nobel Prize for their discovery that mature human cells can be converted to pluripotent stem cells. These cells have the potential to become almost any type of cell in the body.

"These cells have since been used to create vascular cells, brain cells and kidney cells, but they have not yet been successful with the salivary glands," Andreadis says.

Organoids integrate into mouse salivary glands

Baker's research team in Missouri transplanted the organoids into the submandibular salivary glands of immunodeficient mice, which allowed the human-derived tissue to be studied without immune rejection. Andreadis and the UB team then performed the immunostaining and analyzed how well the transplanted organoids integrated and differentiated within the host tissue.

They discovered that after more than 40 days in mice, the transplanted organoids not only survived but also integrated into the existing salivary gland tissue.

Further analysis showed that the organoids contained cells that are present in more mature glands, including acinar cells, which produce saliva; ductal cells, which carry saliva to the mouth; and myoepithelial cells, which help squeeze saliva out of the glands.

"These newly formed glands looked similar to native salivary glands and even developed lumens, or the hollow spaces where saliva would normally flow," Andreadis says.

Refining cells for future transplantation

The team plans to further refine the differentiation process so that the cells comprising the organoids become more mature and their developmental fate can be more precisely controlled.

"Basically, our experiments so far showed that the transplanted organoids have the potential to survive in vivo," Sherwood says. "They integrated with the gland of the mouse and differentiated to include major salivary gland structures. This means they could, potentially, become a renewable source of replacement cells in patients in the future."

The team is also working to determine the best stage of organoid development for transplantation and to improve the conditions in which the organoids grow. The goal is to help them produce more saliva and connect properly with the existing ducts that carry saliva to the mouth, as well as with the nerves that control salivary gland function.

"While using these cells in humans is a long way off, this research does suggest that one day scientists could repair salivary glands damaged by radiation therapy, restore saliva production in people with chronic dry mouth, study diseases of the salivary glands in the lab and test potential new drugs on human salivary tissue," Andreadis says.