Patients with severe chronic dry mouth caused by radiation therapy and Sjögren’s disease may eventually have access to regenerative treatments after University at Buffalo researchers grew salivary gland mini-organs from human pluripotent stem cells, according to a study published September 17 in Nature Communications.
Extreme dry mouth makes speaking, swallowing, and eating difficult. Conventional methods like stimulating natural saliva production or creating artificial substitutes have largely fallen short.
Stem Cells Create Salivary Organoids
Salivary glands had remained out of reach for researchers until now. The team used human pluripotent stem cells, which can be sourced easily from adult tissue like skin or blood.
The cells produced salivary gland epithelial progenitor cells that self-organized within three-dimensional hydrogels into tiny organoids recreating key steps of normal gland development.
“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.”
Stelios Andreadis, Co-Principal Investigator
Transplants Succeed in Mice
Researchers including Kihoon Nam, Frank Maslow, and Travis Small performed the transplantation studies in the Olga Baker laboratory at the University of Missouri-Columbia. A bioinformatics team involving Sai Harsha B. Bhamidipati led the analysis with help from Yali Zhang and Jianmin Wang in the Song Liu laboratory at Roswell Park Comprehensive Cancer Center.
The team examined the tissue using immunostaining after more than 40 days in mice to analyze how well the transplanted organoids integrated and differentiated within the host tissue.
“Basically, our experiments so far showed that the transplanted organoids have the potential to survive in vivo. 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.”
Laura Sherwood, Biomedical Engineering Doctoral Candidate at the University at Buffalo
Organoids Mimic Native Tissue
Microscopic analysis confirmed that the integrated organoids developed key structural features of native tissue, displaying lumens where saliva would normally flow.
- Acinar cells, which produce saliva.
- Ductal cells that transport saliva to the mouth through newly formed hollow spaces called lumens.
- Myoepithelial cells that help expel saliva from glands.
Researchers Target Clinical Use
Clinical application in humans is distant. The team’s next steps involve refining differentiation protocols, as the findings suggest salivary gland organoids hold promise for studying salivary gland development, disease progression, drug screening, and the development of cell therapies for regeneration.
Investigators are examining how to help patients produce more saliva and connect properly with existing ducts that carry saliva to the mouth, as well as with the nerves that control salivary gland function.
None of the current studies establish a timeline for human clinical trials.