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Salivary organoids grown from human stem cells survive more than 40 days in mouse glands
University at Buffalo researchers grew salivary organoids from human stem cells that survived and integrated in mouse glands for over 40 days. The goal is replacement tissue for radiation and Sjögren's dry mouth, where gland stimulation and artificial saliva have fallen short.
The Scientist · Science desk
What happened
- The study, published in Nature Communications, was co-led by Stelios Andreadis at Buffalo and Olga Baker at the University of Missouri School of Medicine.
- The team guided the stem cells through steps that mimic how salivary glands form, yielding progenitor cells that organized themselves into three-dimensional organoids.
- Baker's group transplanted the organoids into the submandibular glands of immunodeficient mice so the human tissue would not be rejected, and the Buffalo team analyzed the grafts.
- The grafts contained acinar cells that make saliva, ductal cells that carry it, and myoepithelial cells that help squeeze it out of the gland.
- The researchers plan to refine the differentiation process so the organoid cells mature further and their developmental fate can be controlled more precisely.
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Why it matters
- constraint Until someone measures secretion from a graft in a damaged gland, the organoids cannot be weighed as a treatment against artificial saliva or gland stimulation.
- exposure In a Sjögren's patient, a graft would meet an immune system already attacking salivary tissue. The immunodeficient mice did not model that.
- capability If the organoids hold up, labs could use them as a human salivary tissue model for disease and drug-screening work well before any transplant reaches a patient, as Andreadis suggests.
Andreadis's case for starting from pluripotent cells is practical. "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," he said [4]. Salivary tissue had been a gap in what those cells could make. "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," he said [8].
He described the grafts in structural terms. "These newly formed glands looked similar to native salivary glands and even developed lumens, or the hollow spaces where saliva would normally flow," Andreadis said [12].
The thing this doesn't tell you is whether any saliva flowed. The account does not report a measurement of saliva output, the number of mice, or whether the host glands had been injured before the transplant [1]. Dry mouth this severe hampers speaking, swallowing and eating, so secretion is the outcome a patient would notice [1]. Laura Sherwood, a doctoral candidate and co-first author with Ronel Samuel, kept the claim narrow [6]. "Basically, our experiments so far showed that the transplanted organoids have the potential to survive in vivo," she said [13].
The immunodeficient hosts took the immune system out of the experiment by design [9]. That matters most for Sjögren's, which the account groups with autoimmune diseases [1]. Andreadis's route to the clinic runs through cells taken from a patient's own skin or blood [4]. These mice cannot show whether tissue grown from those cells would last in a body already attacking its salivary glands [9].
I think this is a credible engraftment result but an early therapy result. It stays early until a graft is shown to secrete saliva inside an injured gland. Andreadis also pointed to uses that ask less of the tissue. The 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," he said [16].
What to watch
- A follow-up that measures saliva secretion from grafted organoids in mice whose glands were first damaged by radiation.
- Transplants into animals with intact immune systems, or organoids made from cells of Sjögren's patients, to test how grafts fare against immune attack.
- Whether the refined differentiation process produces more mature organoid cells whose fate the team can control.