3D Tear Duct ‘Mini Organs’ Could Help Advance Research Into Dry Eyes

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by Lindsey Shapiro PhD |

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A research team in Japan has developed three-dimensional (3D) “mini organs” from human stem cells to model the lacrimal glands, or tear ducts, which are dysfunctional in Sjögren’s syndrome.

The first of their kind, these new mini organs, or organoids, can be used in the future to study disease mechanisms and develop new treatments for Sjögren’s syndrome and other diseases characterized by eye dryness.

“This advance holds promise for future studies of lacrimal gland development and for use in future regenerative therapies to treat disorders such as Sjögren’s syndrome,” the researchers wrote in their study, “Generation of 3D lacrimal gland organoids from human pluripotent stem cells,” which was published in the journal Nature. 

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The production of organoids derived from human stem cells has become an increasingly popular approach to studying human organ function and disease processes. Stem cells are able to give rise to all other cell types found in the body.

In cell cultures, stem cells can be treated with different molecules to stimulate them to form tiny organ-like structures that mimic the behavior of the human organ they correspond to. Organoids of the brain, kidney, lungs, and other organs have already been created by scientists.

Lacrimal glands are responsible for producing tears that are needed to lubricate and protect the eyes. In Sjögren’s, these glands are the target of a misdirected autoimmune attack, leading to decreased tear production and chronic dry eyes.

Previously, a team led by researchers at Osaka University in Japan developed two-dimensional (2D) eye-like organoids. The scientists found that these structures contained cells that appeared to be precursors, or progenitors, to lacrimal gland cells.

“We found that further culture of this progenitor cell population, which expressed early markers of lacrimal gland development, resulted in the successful formation of 3D lacrimal gland organoids,” Ryuhei Hayashi, PhD, the study’s first author, said in a press release.

These organoids had a cellular organization similar to human lacrimal glands, and contained proteins that are necessary for lacrimal gland development.

When transplanted into rats whose own lacrimal glands had been partially or completely removed, the organoids showed signs that they were continuing to develop into mature lacrimal gland tissue, including the expression, or production, of proteins related to tear production.

“We were pleased to find that post-transplantation, the organoids demonstrated differentiation into mature lacrimal gland tissue,” said Kohji Nishida, MD, PhD, the study’s senior author.

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The importance of the findings is far-reaching, the researchers noted.

In the future, organoids can be used to more closely study lacrimal gland development and dysfunction in disease. For example, if stem cells from patients with a disease like Sjögren’s are used to develop the organoids, specific mechanisms of the disease can be more closely — and potentially more accurately — studied.

The technology could also be applied to develop a therapeutic approach for regenerating lacrimal gland tissue in Sjögren’s patients and others with dry eye disease, once the right surgical procedure has been optimized, the team noted.