The quest for a saliva biobank
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Most of us don’t think twice about saliva, until it’s gone. This clear fluid, produced by our salivary glands, keeps our mouths moist, helps us taste food, makes swallowing easier, and even guards against tooth decay and infections. But for millions of people worldwide, this basic function is disrupted. Cancer patients treated with head and neck radiation, individuals with autoimmune conditions like Sjögren’s syndrome, and even those on certain common medications often suffer from chronic dry mouth, or **xerostomia**.
It’s more than a nuisance: without enough saliva, eating becomes painful, speech is difficult, and the risk of dental problems and infections skyrockets. Yet, despite decades of research, medicine still has no reliable way to restore fully functioning salivary glands once they’ve been damaged. That may be about to change.
In a study published in [npj Regenerative Medicine], a team of scientists at **Mayo Clinic**, **University of Michigan** and **University Medical Center Groningen** unveiled the first large, clinically annotated **biobank of salivary tissue organoids**, tiny, lab-grown structures that mimic the architecture and function of real glands. Think of them as miniature stand-ins for the real thing, preserved and ready to help researchers unlock the secrets of regeneration.
The major salivary glands, parotid, submandibular, and sublingual, work in harmony to keep our mouths healthy. But once radiation, disease, or aging disrupts them, today’s treatments can only go so far. Artificial saliva sprays provide fleeting relief, and drugs like pilocarpine stimulate whatever gland tissue remains, but they can’t replace what’s lost.
Scientists have long wondered: could stem cells, the body’s natural repair toolkit, be coaxed into rebuilding salivary glands? Animal studies suggested it was possible, but progress was hampered by a glaring problem: the lack of a reliable, shared supply of high-quality human tissue to study. That’s where the research team, consisting of Dr. Nagarajan Kannan, Dr. Jeffrey Janus, and Dr. Akhilesh Pandey, stepped in. They realized that to crack the puzzle of salivary regeneration, they first needed to build a **library of living salivary tissues** that any researcher could study.
The new biobank wasn’t created overnight. Between 2020 and 2024, the team carefully collected tissue samples from **208 donors**, both living patients undergoing head and neck surgeries and deceased individuals through autopsies. Each gland was processed, broken down into fragments, and preserved as **“tissue organoids”**, three-dimensional cell clusters that retain the essential features of the original gland. When cultured in the lab, these organoids spring back to life, growing and differentiating into various cell types. In total, the team produced over **2,000 organoid vials**, creating what may be the most comprehensive salivary gland resource in the world. The biobank is also meticulously annotated. Each sample is linked to clinical data, age, sex, health history, cancer treatment exposure, even COVID-19 infection, providing an unparalleled opportunity to explore how different conditions affect salivary biology.
The question at the heart of this work is **where do the stem and progenitor cells that can regenerate salivary tissue actually come from?** Using sophisticated tools like **flow cytometry** and **single-cell proteomics**, the researchers identified a population of cells marked by three surface proteins, **CD24, EpCAM, and CD49f**. These cells, they found, were capable of proliferating and forming new organoids, making them strong candidates for the elusive **salivary gland stem/progenitor cells (SGSPCs)**.
But as these cells matured, they began expressing a protein called **PSMA (Prostate-Specific Membrane Antigen)**, also known as **FOLH1**. PSMA is infamous in oncology circles as the target of new prostate cancer drugs and imaging techniques. Yet here, the team showed it also acts as a **marker of differentiation** in salivary glands. In other words, PSMA-negative cells were the stem-like progenitors, while PSMA-positive cells had taken on specialized, secretory roles.
This insight has practical importance: PSMA-targeted therapies, which are revolutionizing prostate cancer treatment, often damage salivary glands as a side effect. Knowing that PSMA plays a role in gland maturation helps explain why, and could guide ways to protect the glands in future treatments.
To go deeper, the researchers turned to **single-cell proteomics**, a cutting-edge technology that profiles thousands of proteins in individual cells. By doing so, they mapped out more than **2,400 proteins** across hundreds of salivary gland progenitors.
Among the discoveries were **unique keratin proteins**, which act as structural scaffolds in cells, and **peroxiredoxins**, enzymes that regulate oxidative stress. Intriguingly, the progenitor cells seemed to thrive when exposed to low levels of hydrogen peroxide, suggesting that a little oxidative stress may actually fuel their growth. This could be a key clue in understanding how glands maintain balance and respond to injury.
Dry mouth may sound minor compared to heart disease or cancer, but for patients living with it, the impact is profound. Imagine struggling to chew a sandwich, choking on dry food, or being unable to speak comfortably in public. For cancer survivors, it’s often a lifelong reminder of their treatment. By creating a **living library of salivary gland organoids**, the Mayo team has laid the foundation for therapies that don’t just mask symptoms but **restore function**. One day, patients could receive transplants of lab-grown salivary tissue or stem-cell–based therapies tailored to their condition. The work also has ripple effects beyond dentistry and oncology. Because salivary glands are accessible and well-defined, they may serve as a model system for studying regeneration in other epithelial organs, from the pancreas to the lungs.
With clinical trials of salivary stem-cell transplants already underway in Europe, and now a robust U.S.-based biobank, the path from lab bench to bedside is becoming clearer. A few questions remain. For instance, can these lab-grown organoids truly replace damaged glands inside the body? How can we scale up production safely for patients? And will the regenerative capacity of these cells hold up over decades? But what’s clear is this: we’re witnessing the dawn of a new era in regenerative medicine. For the first time, patients suffering from chronic dry mouth may have reason to hope for restoration.
If you want to learn more, read the original article titled "Establishment of salivary tissue-organoid biorepository: characterizing salivary gland stem/progenitor cells and novel differentiation marker PSMA/FOLH1" on [npj regenerative medicine] at .
[npj regenerative medicine]: https://doi.org/10.1038/s41536-025-00410-5