Scientists develop salivary glands from stem cells

October 16, 2018

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 revolutionary findings were published in the journal Nature Communications.

Salivary glands digest starch and facilitate swallowing, and can sometimes 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,” said the authors.

“Salivary glands play an essential role in oral health, and the reduction of saliva flow causes deterioration of the quality of life.”

Total regrowth of a lost organ would be the best solution. However, the process is difficult because organogenesis is a complex process that involves special stem cells that need to become specific tissues.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, although the process involves complicated chemical signaling and changes in gene expression.

Scientists have identified Sox9 and Foxc1 as the two key transcription factors ultimately differentiate the stem cells into salivary gland tissue. They also identified the chemicals,FGF7 and FGF10,to induce 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.

The researchers implanted the organoids into mice without saliva glands with mesenchymal tissue, which forms the connecting material that allows the glands to attach to other tissues, and tested them by feeding them citric acid. The combination allowed proper connection to the nerve tissue, secreting a substance that very similar to real saliva.

“It was incredibly exciting to see that the tissues we created actually functioned in a living animal,” Mishima said.

“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,” he said.

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