Scientists from Japan have regenerated fully functioning bioengineered salivary and tear glands, according to two reviews published in the journal Nature Communications.

Researchers from the Tokyo University of Science, led by professor Takashi Tsuji, say their findings demonstrate proof-of-concept and indicate a big step toward next-generation organ replacement regenerative therapies, helping people whose organs have been damaged by disease, injury or aging.

For both studies, the researchers transplanted and tested their regenerated glands in mouse models that had certain disorders.

The mice who underwent salivary gland transplantation had a disorder known as xerostomia, while the mice who had the tear gland transplantation suffered from a forn of dry eye disease (DED).

“Many people are affected by dry mouth or dry eye,” Miho Ogawa, researcher at the Tokyo University of Science told Medical News Today.

“Current therapies for these diseases can temporarily increase the flow rate of saliva or tear, but cannot restore the secretory gland function. Therefore, a novel therapeutic treatment for the restoration of secretory gland function is needed.”

The fully functional bioengineered salivary gland was created in order to combat salivary gland hypofunction, known as xerostomia. This condition occurs as a result of radiation therapy for head cancer. It can cause many oral health issues, including dental decay, bacterial infection and swallowing dysfunction.

With this is mind, the researchers regenerated a fully functional salivary gland through orthotopic transplantation of a bioengineered salivary gland germ.

The researchers explain that the bioengineered germ developed into a mature gland. Tested in a mouse model, the gland was able to produce saliva in response to pilocarpin – a drug used to treat dry mouth – and stimulation through citrate. The gland was also found to protect against oral infection and restored normal swallowing.

The study authors explain:

The bioengineered submandibular gland, which was transplanted using an inter-epithelial tissue-connecting plastic method, produced saliva in response to the administration of gustatory stimulation by citrate, protected against oral bacterial infection and restored swallowing in a mouse model of a salivary gland defect.

Thus, this study provides a proof-of-concept for bioengineered salivary gland regeneration as a potential treatment of xerostomia.”

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Researchers created fully functional bioengineered lacrimal and harderian glands of the eye, which were shown to secrete tears and protect the eye surface in mouse models.
Photo credit: Tsuji et al.

Another study details the researcher’s creation of a fully functional bioengineered lacrimal gland and a harderian gland. The glands play an important role in maintaining a healthy eye surface through tear secretion.

The researchers transplanted and tested the regenerated glands on mice who had extra-orbital lacrimal gland defect – a condition similar to dry eye disease in humans.

The disorder is caused by lacrimal gland dysfunction leading to tear shortage. Long term, the condition can cause damage to the cornea and result in loss of vision.

The scientists created a bioengineered lacrimal gland germ and harderian gland germ, which were both developed in vivo. The glands demonstrated full functioning, including tear production in response to nervous stimulation to the eye, and protection of the eye’s surface.

The researchers say:

This study is the first to demonstrate the potential for bioengineered organ replacement to functionally restore the lacrimal gland.

In addition, we provided proof-of-concept for lipid secretory organ regeneration by regenerating the harderian gland, which secretes lipids that are critical for tear function.”

The researchers say that the next step is to use their findings for clinical application. But Ogawa told Medical News Today that several problems must be solved before the use of bioengineered secretary glands becomes feasible:

“One of the most important things is to identify the suitable cell sources. Our research group is currently attempting to induce bioengineered organ germ to develop a fully functioning organ using embryonic organ germ-derived epithelial and mesenchymal cells via the Organ Germ Method.”

“In the future,” he continues, “we will need to identify cell sources from various tissue-derived stem cell populations isolated from patients who have the organ-inducible ability to reproduce the epithelial and mesenchymal interactions for organogenesis.”

Further investigation of the clinical application of these methods, including engraftment and recipient niches for organ regeneration, will contribute to the development of salivary gland regeneration therapy in humans.”