University at Buffalo researchers have developed salivary gland organoids from human pluripotent stem cells, an approach that could eventually provide new ways to study and potentially treat severe dry mouth caused by cancer therapy and autoimmune diseases such as Sjögren’s disease.
The research, published September 17 in Nature Communications, focuses on creating salivary gland tissue from pluripotent stem cells derived from accessible adult cells such as skin or blood cells.
Researchers guided the cells through developmental stages that produced salivary gland epithelial progenitor cells. Those cells then organized into three-dimensional structures known as organoids, or mini organs.
The research was led by co-principal investigators Stelios Andreadis of the University at Buffalo and Olga Baker of the University of Missouri School of Medicine. UB biomedical engineering doctoral candidate Laura Sherwood and Ronel Samuel were co-first authors.
Researchers at Missouri transplanted the organoids into the submandibular salivary glands of immunodeficient mice. The UB team then studied how the transplanted human-derived organoids integrated and differentiated.
After more than 40 days, the organoids survived and integrated into existing salivary gland tissue.
Analysis found that the transplanted structures contained several cell types associated with mature salivary glands, including saliva-producing acinar cells, ductal cells that transport saliva and myoepithelial cells that help expel saliva from glands.
The researchers also observed lumens, the hollow spaces through which saliva would normally flow.
The team now plans to refine the differentiation process, improve maturation of the organoids and determine the best developmental stage for transplantation.
Researchers are also studying how to improve saliva production and connect transplanted organoids with existing ducts and nerves.
Potential future applications include regenerative cell therapies, disease modeling and drug screening. The researchers cautioned that human therapeutic use remains a long-term goal.
KEY QUOTES:
“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.”
“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.”
“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.”
“These newly formed glands looked similar to native salivary glands and even developed lumens, or the hollow spaces where saliva would normally flow.”
“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.”
Stelios Andreadis, SUNY Distinguished Professor at the University at Buffalo
“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, Ph.D. Candidate in Biomedical Engineering at the University at Buffalo
