Salivary/Lacrimal Gland Regeneration
Salivary/Lacrimal Gland Regeneration

Awaiting a radical cure for secretory gland dysfunction

Awaiting a radical cure for secretory gland dysfunction Secretory glands play crucial roles in the maintenance of homeostasis in living organisms. They can be divided into endocrine glands, which release hormones into peripheral blood, and exocrine glands, which produce and carry saliva, tears, or other bodily fluids. The salivary glands belong to the latter. The saliva they release plays a role in the digestion of food, oral hygiene, disinfection, and dentin protection. The tears released by the lacrimal glands play a vital role in protecting corneal epithelial cells on the eye surface. Numerous factors can disrupt the normal physiological activity of these glands, such as aging, stress, autoimmune disease, and radiotherapy for cancer treatment. Dry mouth due to salivary gland dysfunction can lead to infections or difficulty swallowing (dysphagia). Likewise, dry eye due to lacrimal gland dysfunction can damage those epithelial cells, causing discomfort and serious vision loss. A severe decline in quality of life can accompany these changes in every case.
There is real demand for curative therapies for exocrine hyposecretion. Most modern treatments are symptomatic in nature, compensating with artificial fluids such as saliva substitutes or eye drops. We are currently developing technology to regrow salivary and lacrimal glands to make the dream of exocrine gland regeneration a reality.

Salivary gland regeneration

Similar to other organs, salivary gland development is guided by interactions between epithelial and mesenchymal stem cells. Our approach involves growing salivary gland germ using the organ germ method, which connects with salivary ducts, the conduits for saliva into the oral cavity, as it grows, replicating the tissue’s natural structure. This approach completely restored salivary function in a dysphagia mouse model whose salivary glands were completely removed. Our work demonstrates the feasibility of orthotopic transplantation of regenerated salivary glands as a new treatment for dry mouth.

Lacrimal gland regeneration

Our approach to regenerating lacrimal glands is similar in many regards. Once implanted in the body, lacrimal gland germ develops a tissue structure comparable to its natural structure, including connections with nerve fibers in the periphery. Model mice treated using this approach produced the same amount of tears in response to external stimulation as those of normal mice. Moreover, they had significant improvements in eye surface damage and corneal epithelium thickness, attaining levels comparable to those of healthy mice. Our work demonstrates the potential of orthotropic transplantation of regenerated lacrimal gland as a novel treatment for dry eye.

R&D for clinical applications of secretory gland regeneration

Finding suitable seed cell populations is a major theme in organ regenerative medicine today. To this end, we are developing new technologies to induce lacrimal gland formation from induced pluripotent stem cells (A-MED, Research Center Network for Realization of Regenerative Medicine).