These miniature tear glands grown from stem cells can cry

March 16, 2021

Dry eye may have an implantable cure. (Unsplash/Kajetan Sumila)

Scientists grew miniature versions of tear glands from human and mouse stem cells that can successfully produce tears, saying that future versions of these lab-grown tissues could eventually be transplanted into people with malfunctioning tear glands.

The researchers reported their findings Tuesday in Cell Stem Cell, noting that they were able to successfully transplant their tear gland organoids into mice. 

"This is an important first step for potential regenerative therapies," the researchers wrote in the study. "However, we did not show that organoid engraftment could restore [tear] gland function."

Tear glands secrete several kinds of tears to keep the eyes moist and protect them from damage. When they aren't working properly, as in dry eye disease or Sjögren's syndrome, an autoimmune condition known by some for its impact on professional tennis player Venus Williams, the consequences can range from itchy or burning eyes to blurry vision, damage to the corneas and even blindness without proper treatment. 

Scientists are investigating how organoids — three-dimensional tissue cultures grown from stem cells to mimic aspects of organs such as the thyroid, gut and salivary glands — can be used to learn about how the organs work normally and in diseases such as cancer. 

Transplanted organoids also show promise as a treatment for certain illnesses, says Hans Clevers, a group leader at the Hubrecht Institute for Developmental Biology and Stem Cell Research in the Netherlands and last author of the new study. One clinical trial to investigate transplanting salivary gland organoids into people experiencing dry mouth after radiation for head and neck cancers is set to begin this summer, he points out.

However, as the study notes regarding mini-tear glands,"Additional validation of the beneficial effects of organoid transplantation in mouse models of dry eye disease is required."

Organoids can be grown from pluripotent stem cells or adult stem cells, which are found in most adult tissues

"Normally these stem cells function to maintain organs; when cells are lost, they replace them," Clevers said. "Some tissues do this constantly, like the skin or the gut."

To recreate mouse and human tear glands, Clevers and his team used methods they'd previously developed to grow other organoids from adult stem cells. For the human organoids, the researchers used cells from leftover tear gland tissue samples donated by people undergoing biopsies or other surgeries. 

Once they had grown the mini-tear glands, the team tested whether they could actually cry. The researchers exposed the organoids to some of the same chemical messengers that normally prompt the glands to begin making tears when released by nearby nerves. Because these organoids couldn't drain the fluid like proper tear glands, they swelled up.

"Organoids normally don't move," Clevers said. "So to see, actually in real time see, tears being formed — that was special."

These findings indicate that tear gland organoids could also be used to screen tear-inducing drugs to treat conditions such as dry eye disease and Sjögren's syndrome.

In another experiment, the team used gene editing to prevent a gene that is crucial for eye development from being expressed in the organoids. 

"Then essentially what we have is an organoid that still grows, but it's just a gland; it no longer looks like a tear gland," Clevers said. "We just wanted to show that [the organoids] are amenable to gene editing."

The tiny organoids did not reproduce every part of the tear glands. In the future, Clevers said, the team will strive to create an "even more complete" organoid.

The study, "Exploring the human lacrimal gland using organoids and single-cell sequencing," published March 16 in Cell Stem Cell, was authored by Marie Bannier-Hélaouët, Jeroen Korving, Marc Trani Bustos, Harry Begthel, Yotam E. Bar-Ephraim, Jelte van der Vaart and Hans Clevers, Hubrecht Institute; Yorick Post, Hubrecht Institute and Surrozen, Inc.; Helmuth Gehart, Hubrecht Institute and ETH Zurich; and Rachel Kalmann and Saskia M. Imhoff, University Medical Center Utrecht.

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