Stem Cell Grown Salivary Glands Offer Hope for Dry Mouth Sufferers

For millions of people living with chronic dry mouth, the simple acts of speaking, swallowing and eating a meal can become daily struggles. Extreme dry mouth, known clinically as xerostomia, arises most often as a consequence of radiation therapy for head and neck cancers and from autoimmune conditions such as Sjögren’s disease, in which the immune system gradually destroys the moisture-producing glands. For years, clinicians have had little to offer these patients beyond palliative measures. Attempts to stimulate the remaining salivary glands to produce more saliva, or to substitute function with artificial saliva products, have proven largely ineffective. Now a research team at the University at Buffalo, working with collaborators at the University of Missouri and Roswell Park Comprehensive Cancer Center, reports a strategy that could fundamentally change the outlook: growing functional salivary gland tissue from human pluripotent stem cells and transplanting it into the mouth.

The study, published on September 17 in the journal Nature Communications, describes how the researchers guided human pluripotent stem cells, or PSCs, through a sequence of developmental steps that mirror the way salivary glands form naturally during human embryonic development. Stelios Andreadis, PhD, SUNY Distinguished Professor in the Department of Chemical and Biological Engineering in the School of Engineering and Applied Sciences at the University at Buffalo, serves as co-principal investigator on the study alongside Olga Baker, PhD, DDS, a professor in the Department of Otolaryngology at the University of Missouri School of Medicine in Columbia. Andreadis also directs UB’s Center of Cell, Gene and Tissue Engineering and is a member of the UB Center of Excellence in Bioinformatics and Life Sciences.

The appeal of pluripotent stem cells as a starting material lies in their remarkable accessibility and versatility. Human pluripotent stem cells can be derived from easily obtainable adult somatic cells, such as skin or blood cells, and then reprogrammed into a state in which they retain the potential to become almost any cell type in the body. That reprogramming concept earned Shinya Yamanaka of Japan and the late British biologist John Gurdon the Nobel Prize in 2012, and in the years since, researchers have used the technique to generate vascular cells, brain cells and kidney cells for study and potential therapy. Salivary gland tissue, however, had remained an elusive target, largely because of the intricate architecture and multiple specialized cell types that a working gland requires.

The Buffalo team’s approach centers on coaxing the pluripotent stem cells into becoming salivary gland epithelial progenitor cells, abbreviated SGEPs. These progenitors then organize themselves spontaneously into tiny three-dimensional structures known as organoids, miniature versions of organs that recapitulate key features of native tissue in the laboratory. Organoids have become one of the most powerful tools in modern biomedical research because they allow scientists to study organ development, disease progression and drug responses in a dish, using human-derived tissue rather than simplified cell cultures. According to Andreadis, the findings suggest that salivary gland organoids may hold promise not only for studying salivary gland development, disease progression and drug screening, but also for the development of cell therapies aimed at regenerating the glands themselves.

Generating the organoids in culture, however, is only half of the challenge. A replacement gland must survive inside a living body, integrate with surrounding tissue and mature into the full complement of functional cell types. To test whether the lab-grown structures could meet that bar, Baker’s research team in Missouri transplanted the organoids into the submandibular salivary glands of immunodeficient mice. The use of immunodeficient animals was a deliberate methodological choice: it allowed the human-derived tissue to be studied in vivo without the complication of immune rejection, giving the researchers a clear window into how the transplanted cells behave in a living glandular environment.

The results were striking. After more than 40 days inside the mice, the transplanted organoids had not merely survived; they had integrated into the existing salivary gland tissue of their hosts. Andreadis and the UB team performed the immunostaining and analyzed how well the grafts had incorporated and differentiated within the host tissue. Further analysis revealed that the organoids contained the cell types found in more mature glands, including acinar cells, which are the workhorses of saliva production; ductal cells, which form the channels that carry saliva from the gland into the mouth; and myoepithelial cells, specialized contractile cells that help squeeze saliva out of the glands and into the ductal network. The presence of all three lineages indicates that the organoids were recapitulating the essential cellular architecture of a functioning gland.

Perhaps most encouraging was the structural maturity the grafts achieved. Andreadis noted that the newly formed glands looked similar to native salivary glands and even developed lumens, the hollow interior spaces through which saliva would normally flow. Lumens are a hallmark of organized epithelial tissue and a prerequisite for any gland that hopes to secrete fluid in a directed way. Their appearance in the transplanted organoids suggests that the developmental program the researchers initiated in culture continued to unfold once the cells were placed in a living environment, driven by cues from the surrounding host tissue.

Laura Sherwood, a PhD candidate in biomedical engineering and a member of Andreadis’s research group, was first author on the paper together with Ronel Samuel, who completed his doctorate in 2024. Sherwood, who earned an award for this research at the 2025 Salivary Glands and Exocrine Biology Gordon Research Conference, summarized the significance of the transplantation experiments plainly. The experiments so far showed that the transplanted organoids have the potential to survive in vivo, she explained, and they integrated with the mouse gland and differentiated to include major salivary gland structures. That combination of survival, integration and differentiation, she noted, means the organoids could potentially become a renewable source of replacement cells for patients in the future.

Considerable work remains before such a therapy could reach the clinic, and the team is pursuing several parallel lines of refinement. One priority is to improve the differentiation process so that the cells composing the organoids become more mature and their developmental fate can be controlled with greater precision. The researchers are also working to determine the optimal stage of organoid development for transplantation and to improve the culture conditions in which the organoids grow. The ultimate functional goals are demanding: the engineered tissue must produce saliva in useful quantities, connect properly with the existing ducts that carry saliva into the mouth, and establish connections with the nerves that regulate salivary gland function. Each of these requirements represents a distinct biological hurdle, from vascularization and innervation to mechanical coupling with the recipient’s own ductal system.

Even with those challenges ahead, the implications of the work extend well beyond a single future therapy. Andreadis observed that while using these cells in humans is a long way off, the research suggests 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 laboratory and test potential new drugs on human salivary tissue. For the patients whose quality of life is most eroded by xerostomia, particularly survivors of head and neck cancer and people living with Sjögren’s disease, the study offers something that has been missing from the field for decades: credible evidence that replacement salivary tissue can be built from a patient-accessible cell source and can take root in a living gland. Other participating researchers included graduate student Sai Harsha Bhamidipati in the UB Department of Chemical and Biomedical Engineering; Kihoon Nam, Frank Maslow and Travis Small with the University of Missouri; and Yali Zhang, Jianmin Wang and Song Liu with the Department of Biostatistics and Bioinformatics at Roswell Park Comprehensive Cancer Center. The researchers reported no conflict of interest.

Subject of Research: Derivation of transplantable salivary gland organoids from human pluripotent stem cells for treating dry mouth

Article Title: UB researchers grow salivary glands from pluripotent stem cells

Article References: UB researchers grow salivary glands from pluripotent stem cells. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: pluripotent stem cells, salivary glands, organoids, xerostomia, Sjögren's disease, regenerative medicine, tissue engineering, radiation therapy, acinar cells, Nature Communications, cell therapy, University at Buffalo