Lab-grown salivary glands offer hope for dry mouth

If you’ve ever had a dry mouth after a long run, during a stressful presentation, or because of certain medications, you know how uncomfortable it can be. Now imagine living with that sensation permanently. That’s the reality for millions of people worldwide who suffer from xerostomia, or chronic dry mouth.

This condition often strikes patients who undergo radiation therapy for head and neck cancers, as well as those with autoimmune diseases like Sjögren’s syndrome. It happens because the body’s salivary glands, which produce the fluid that keeps our mouths moist and healthy, become damaged and stop functioning properly. Unfortunately, once these glands are destroyed, there’s currently no permanent cure.

But a team of researchers at McGill University in Montreal believes they may be on the trail of a solution, and it comes in the form of tiny, lab-grown “mini-glands” cultivated in 3D.

Saliva is so much more than water. It’s a complex cocktail of enzymes, proteins, and electrolytes that does everything from helping us chew and swallow to protecting teeth from decay and washing away harmful bacteria. The star players in this process are specialized cells in the glands called acinar cells, which are essentially nature’s fluid factories.

The problem is that acinar cells are extremely fragile. They don’t divide and replenish themselves easily, and once they’re gone, they’re nearly impossible to replace. Scientists have long dreamed of creating lab-grown salivary tissues that could be transplanted into patients, but keeping acinar cells alive and functional outside the body has proven to be one of biomedical science’s tougher challenges.

That’s where the McGill team, featuring researchers in Dental Medicine, Oral Health Sciences, Bioengineering, and Materials science, comes in. They tried to answer the question: What if we could grow acinar cells in an environment that mimics their natural home inside the body?

To test this, the researchers, that is, Jose G. Munguia-Lopez, Sangeeth Pillai, Yuli Zhang, Amatzia Gantz, Dimitria B. Camasao, Showan N. Nazhat, and Joseph M. Kinsella, turned to hydrogels. These are water-rich materials that feel a bit like soft Jell-O, and they’re widely used in biomedical research because they can mimic the squishy, supportive environment cells normally live in.

The team compared three different types of reversible, 3D hydrogels: Alginate–gelatin (AG), Alginate–gelatin with collagen (AGC), and Alginate–gelatin with hyaluronic acid (AGHA). All of them were designed to imitate the texture and flexibility of real human salivary tissue.

When the researchers placed human salivary acinar cells into these gels, something remarkable happened: the cells began to self-assemble into tiny spherical clusters, known as spheroids. Think of them as miniature versions of the gland’s working units.

But not all gels worked equally well. The superstar was the AGHA hydrogel, the one containing hyaluronic acid, a molecule you might recognize from skincare products, where it helps retain moisture.

In the lab, AGHA created the most life-like results. In fact, the spheroids grew larger than 100 cells each. More than 93% of the cells stayed alive and healthy after two weeks. They continued to produce key salivary proteins, such as aquaporin-5 (a water channel), NKCC1 (an ion transporter), ZO-1 (a junction protein), and α-amylase (the enzyme that starts digesting starch). Even more impressively, the spheroids responded to stimulation by releasing enzyme-packed granules, just like real glands do when you taste food.

In other words, the cells were actually acting like real salivary glands.

One might ask: why did the AGHA hydrogel work so much better than the others? The answer lies in the fact that biology loves the familiar. Acinar cells naturally carry receptors (called CD44) that recognize and bind to hyaluronic acid. By adding this molecule to the hydrogel, the researchers gave the cells a signal that said: You’re home. It’s safe to grow and organize. This subtle nudge was enough to help the cells behave more like they do inside the body, forming tight, functional clusters instead of losing their identity.

At first, the experiments were done using an immortalized cell line, basically, a population of acinar cells adapted for long-term growth in labs. But the team also tested their system with primary human salivary cells, real cells taken directly from donated tissue. Again, the AGHA hydrogel supported the growth of functional “salivary functional units” (SFUs) that looked and acted strikingly like natural gland structures.

This is a crucial step, because while immortalized cell lines are useful for proof-of-concept work, it’s the primary cells that matter most when it comes to developing therapies for patients.

For patients with chronic dry mouth, the current options are frustratingly limited. Doctors can prescribe drugs that stimulate whatever acinar cells remain, but these only help temporarily. Others rely on palliative measures, like special rinses or saliva substitutes, which ease symptoms but don’t restore the glands’ actual function.

What this new work offers is something different: a platform that could eventually be used to grow replacement salivary tissues in the lab. The uses are many. For instance, a cancer survivor whose salivary glands were damaged by radiation could receive a transplant of lab-grown, functional gland tissue. Also, researchers could use these spheroids as disease models, testing new drugs for conditions like Sjögren’s syndrome in a realistic setting without needing to experiment directly on patients. Furthermore, dentists and doctors could have better tools to study how oral health links to digestion, immunity, and even mental well-being, areas where saliva plays a surprisingly big role.

Of course, these lab-grown spheroids are promising, but they’re still a long way from being fully functional glands with ducts, blood vessels, and connections to nerves. Future research will need to incorporate more cell types and build complex, integrated tissue systems.

But what makes this study exciting is that it shows a low-cost, reproducible, and reversible method for growing these spheroids. Because the hydrogels can be dissolved quickly without damaging the cells, researchers can easily retrieve intact, viable spheroids for further study or even transplantation research.

Science often progresses in small, steady steps rather than dramatic leaps. Growing tiny salivary gland spheroids in a gel may not sound as flashy as designing a rocket or curing a major disease. But for the millions of people whose daily lives are shaped by the constant discomfort of dry mouth, this quiet achievement could one day mean the return of something we all take for granted: the simple relief of saliva.

And that, as it turns out, is a very big deal.

If you want to learn more, read the original article titled "Expansion of functional human salivary acinar cell spheroids with reversible thermo-ionically crosslinked 3D hydrogels" on International Journal of Oral Science at http://dx.doi.org/10.1038/s41368-025-00368-6.