Stop sobbing – because scientists can do it for you. Using stem cells, Dutch researchers have grown miniature human tear glands that can ‘cry’.
Initially, when scientists wanted to develop this technology, their first port of call was the inside of the gut, as it replaces itself 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 multiply rapidly.
“But to our surprise, the stem cells created a mini-organ … it’s small, but it has all the different cells in the gut that you need to digest food,” said study author Hans Clevers, group leader at the Hubrecht Institute for Developmental Biology. and stem cell research and at the Princess Máxima Center for pediatric oncology.
That was in 2009. Since then, researchers have been creating mini versions – called organoids – of the liver, pancreas, bladder, and more. They have even moved from mammals to reptiles and have successfully grown snake venom glands. Last year, Clevers’ PhD students chose to work on human tear glands.
After they first successfully made 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 broke it into small pieces and fed it a bit more to make several mini glands. “They looked like little balloons,” said Clevers.
Lacrimal glands are useful to their human host in many ways. They produce a thin layer of fluid that envelops the cornea, lubricates the surface of the eye, protects it from irritants, and supplies infections and nutrients. The glands are also responsible for producing tears, whether it is physical provocation, such as when someone puts a nail in your eye, or emotional anguish, caused by, say, a car running over your cat. In either case, the brain instructs the tear glands to cry.
“The chemical message coming from the neurons… to your tear glands is adrenaline. So to really show that we had functional tear glands, we had to show that they would respond to adrenaline, ”said Clevers.
When the mini organs were given a sustained supply of the growth factor cocktail, they did not produce much tear fluid upon encountering adrenaline. But once they were cut from the sap, the cells stopped dividing and were allowed to settle down and mature – the adrenaline quickly produced tears, he explained.
The small balloon-like glands quickly became swollen because there were no channels through which the fluid could escape. They eventually had to rip or tear themselves, dribbling some liquid in the form of droplets, Clevers added.
The model has some limitations. The researchers captured one cell – the ductal cell – that makes up the lacrimal gland, but the glands also contain other cells. In addition, these organoids are not part of the human body – in which tear glands can be wrapped by muscles and blood vessels – so there are limitations to their function, he cautioned.
“It’s a reductionist model. But the essence of the lacrimal gland is captured: namely the tear formation and then the adrenaline-induced production of tear droplets. “
This model can now be used by researchers worldwide to identify new drugs for patients who are not producing enough tears and to study how lacrimal gland cancers develop and be treated. Ultimately, this type of organoid could even be transplanted to patients with non-functioning lacrimal glands, the authors suggested in the journal Cell Stem Cell.
Meanwhile, researchers in Clevers’ lab have their next project in mind: crocodile tears.
“We want to grow crocodile tear glands,” says Clevers. “Crocodiles don’t cry because they are sad or something; they are just trying to get rid of salt. That’s why it’s scientifically interesting to really study how this works, how they use their tear glands as kidneys. “