Scientists Create Lab-Grown Salivary Tissue That Responds to Chemical Signals todayheadline

McGill University researchers have developed a new hydrogel system that successfully grows functional salivary gland tissue in the laboratory, offering hope for millions of patients suffering from chronic dry mouth.

The team’s innovative approach uses a special gel containing hyaluronic acid that mimics the natural environment where salivary cells thrive, creating three-dimensional structures that behave remarkably like real salivary glands.

The study, published May 9, 2025, in the International Journal of Oral Science, represents a significant advancement in addressing xerostomia—the medical term for chronic dry mouth that affects patients who’ve undergone radiation therapy for head and neck cancers or those with autoimmune conditions like Sjögren’s syndrome.

A Gel That Mimics Nature

What makes this research particularly compelling is how the scientists solved a fundamental challenge: keeping human salivary cells alive and functional outside the body. Most existing laboratory systems rely on animal-derived materials or chemically fixed matrices that fail to maintain the specialized identity of human acinar cells over time.

The research team tested three different gel formulations, ultimately discovering that their hyaluronic acid-containing version—called AGHA—produced the most promising results. In these gels, salivary cells spontaneously organized into large, spherical clusters containing more than 100 cells each, with over 93% remaining viable.

What’s remarkable about these lab-grown structures is their ability to maintain the molecular machinery essential for saliva production. The cells continued to express key proteins including AQP5, ZO-1, NKCC1, and α-amylase—all critical components of the natural saliva-making process.

Responding Like Real Tissue

Perhaps most importantly, these artificial salivary structures demonstrated functional responsiveness. When researchers exposed them to isoprenaline, a chemical that normally stimulates saliva production, the lab-grown tissue increased its production of α-amylase-containing granules—essentially mimicking what happens in a healthy mouth when you smell your favorite food.

“This study demonstrates that by fine-tuning hydrogel composition, we can closely replicate the native environment of salivary acinar cells,” said Dr. Simon D. Tran, senior author of the study. “Our AGHA-based platform not only supports long-term viability and function, but also enables easy recovery of spheroids without enzymatic damage. This is a significant step forward in developing in vitro models for salivary gland disorders and potential regenerative therapies for patients suffering from chronic dry mouth.”

Beyond the Laboratory Bench

The researchers made an important discovery that wasn’t highlighted in initial announcements: their gel system successfully supported the expansion of primary human salivary cells for up to 15 days. This finding is particularly significant because primary cells—those taken directly from human tissue rather than immortalized cell lines—are notoriously difficult to maintain in laboratory conditions yet are essential for developing clinically relevant treatments.

The mechanical properties of these gels closely match those of natural human salivary gland tissue, measuring approximately 11 kilopascals in stiffness. This biomechanical similarity appears crucial for maintaining the cells’ natural behavior and organization patterns.

Key Advantages of the New System

• Reversible gel matrix allows non-destructive retrieval of intact spheroids
• Eliminates need for animal-derived materials, improving reproducibility
• Supports both immortalized cell lines and primary human cells
• Maintains functional protein expression for extended periods

Clinical Implications

The implications extend far beyond xerostomia treatment. This platform could accelerate the development of disease models, enable high-throughput drug screening, and potentially lead to implantable grafts that restore natural salivary function.

For patients currently managing chronic dry mouth with temporary solutions like saliva-stimulating drugs or palliative care, this research offers a glimpse into more permanent therapeutic options. The ability to grow functional salivary tissue that responds to natural stimuli represents a crucial step toward developing regenerative treatments.

The research team’s approach of using thermo-ionic crosslinking creates what they describe as a “two-phase 3D model” with a partially crosslinked soft core surrounded by a stiffer shell. This unique architecture may explain why the hyaluronic acid-containing gels performed so much better than alternatives containing collagen or basic alginate-gelatin combinations.

Looking Forward

While this represents significant progress, the researchers acknowledge that fully functional saliva secretion will likely require the participation of additional cell types beyond acinar cells. Future work will focus on developing co-culture systems that integrate the complex cellular architecture found in natural salivary glands.

The team’s success with both laboratory cell lines and primary human tissue suggests their platform could serve as a versatile foundation for testing treatments across the spectrum of salivary gland disorders. With this innovation, researchers have moved one step closer to restoring natural salivary function for the millions of patients who need it most.