To cry out loud: Dutch scientists grow human tear glands | Human biology



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Stop sobbing – because scientists can do it for you. Using stem cells, Dutch researchers have developed miniature human tear glands capable of “crying”.

Initially, when scientists were looking to develop this technology, their first port of call was the inner lining of the intestine, as it changed every five days. They took a small piece of intestinal tissue filled with stem cells and fed it with proteins called growth factors to stimulate cell growth, expecting the stem cells to proliferate quickly.

“But to our surprise, the stem cells have created a mini-organ… it’s small, but it contains all of the different gut cells you need to digest food,” the author said. study Hans Clevers, group leader at the Hubrecht Institute for Developmental Biology and Stem Cell Research and the Princess Máxima Center for Pediatric Oncology.

That was in 2009. Since then, researchers have created mini-versions – called organoids – of the liver, pancreas, bladder, and more. They even went from mammals to reptiles, successfully developing snake venom glands. Last year, Clevers doctoral students chose to work on human tear glands.

After successfully creating tear glands for mice, they moved on to human tissue. Suspended in a gel, the tiny piece of donated human tissue was given a cocktail of growth factors. After about a week, the researchers divided it into small pieces and fed it a little more to create several mini-glands. “They looked like little balloons,” Clevers said.

The tear glands are useful to their human host in a number of ways. They produce a thin layer of fluid that envelops the cornea, lubricates the surface of the eye, protects it from irritants and infections, and provides it with nutrients. The glands are also responsible for making tears, whether it is due to a physical provocation, for example, someone puts a nail in your eye, or emotional anguish, caused, for example, by a car. that rolls over your cat. In either case, the brain orders the tear glands to cry.

“The chemical message that comes from neurons… to your tear glands is adrenaline. So to really show that we had working tear glands, we had to show that they would respond to adrenaline, ”Clevers said.

When the mini-organs received a persistent supply of the cocktail of growth factors, they did not produce much tear fluid when they encountered adrenaline. But when cut from the juice, the cells stopped dividing and were allowed to settle and mature – adrenaline quickly produced tears, he explained.

The small balloon-shaped glands quickly inflated because there were no ducts for the fluid to escape. Eventually, they were made to either rupture or rupture on their own, dripping liquid in the form of droplets, Clevers added.

The model has certain limitations. The researchers captured a cell – the duct cell – that the lacrimal gland is made up of, but the glands also include other cells. Moreover, these organoids are not part of the human body – in which the tear glands could be coiled by muscles and blood vessels – so there are limits to their functioning, he warned.

“It’s a reductionist model. But the essence of the lacrimal gland is captured: namely, tear formation, then adrenaline-induced tear droplet production.

This model can now be used by researchers around the world to identify new drugs for patients who do not produce enough tears and to study how lacrimal gland cancers are formed and can be treated. Eventually, this type of organoid may even be transplantable to patients whose tear glands are not functioning, suggest the authors in the journal Cell Stem Cell.

Meanwhile, researchers at Clevers’ lab already have their eye on their next project: crocodile tears.

“We want to grow crocodile tear glands,” Clevers said. “Crocodiles don’t cry because they’re sad or something; they’re just trying to get rid of the salt. That’s why it’s scientifically interesting to really study how it works, how they use their tear glands as kidneys.

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