Salivary gland tissue grown from embryonic stem cells

By Allen Cone
Salivary gland tissue grown from embryonic stem cells
A three-dimensional salivary gland tissue has been grown that produces saliva like normal glands when implanted into mice. Photo by Petr Kratochvil/Public Domain Pictures

Oct. 12 (UPI) -- For the first time, researchers have grown three-dimensional salivary gland tissue that produces saliva like normal glands when implanted into mice.

Scientists from Showa University and the Riken Center for Biosystems Dynamics Research in Japan used embryonic stem cells, which have the ability to transform into many types of cell to create an organoid. The findings were published Thursday in the journal Nature Communications.


Salivary glands, which digest starch and facilitate swallowing, can be damaged by an autoimmune condition known as Sjogren's syndrome as well as radiation therapy for cancer.

"Restoring damaged organ functions and replacing organs with bioengineered organs is expected to be the next-generation of regenerative medicine," the authors wrote. "Salivary glands play an essential role in oral health, and the reduction of saliva flow causes deterioration of the quality of life."

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Although it would be ideal to regrow the lost organ, the process is difficult because organogenesis is a complex process that involves special stem cells that need to become specific tissues, the authors noted.

Except for organs such as hair follicles, those precursor cells are only present during early development.

The actual process of the development of these glands from an early structure called the oral ectoderm is not fully understood. It is known, however, that the process involves complicated chemical signaling and changes in gene expression.

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Scientists have identified two transcription factors -- Sox9 and Foxc1 -- as the key to the differentiation of stem cells into salivary gland tissue. They also identified two chemicals -- FGF7 and FGF10 -- that induced cells to differentiate into salivary gland tissue.

Professor Kenji Mishima of Showa University and Takashi Tsuji of RIKEN BDR first used a cocktail of chemicals that allowed the formation of the oral ectoderm to induce the embryonic stem cells to form the ectoderm.

Then, they used viral vectors to get the cells to express Sox9 and Foxc1. By adding the two chemicals to the mix, they induced the cells to form tissue similar to actual developing salivary glands in the embryo.

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The researchers then implanted the organoids into mice without saliva glands and tested them by feeding them citric acid. They transplanted the organoids with mesenchymal tissue, which forms the connecting material that allows the glands to attach to other tissues.

They found this combination to be properly connected to the nerve tissue, secreting a substance that was remarkably similar to real saliva.

"It was incredibly exciting to see that the tissues we created actually functioned in a living animal," Mishima said in a press release. "This is an important proof of concept that organoids are a valid alternative to actual organs."


Tsuji has been working with other tissues, including hair and skin.

"We continue to work to develop functional tissues to replace the functions of various organs, and we hope that these experiments will soon find their way into the clinic and help patients suffering from a variety of disorders," Tsuji said.

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