Stop your sobbing – because scientists can do it for you. Using stem cells, Dutch researchers have grown miniature human tear glands capable of “crying”.
Initially, when scientists were looking at developing this technology, their first port of call was the inner lining of the gut, because it replaces itself every five days. They took a tiny piece of gut tissue filled with stem cells and fed it proteins called growth factors to stimulate cell growth, expecting the stem cells to rapidly proliferate.
“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 for digesting food,” said the 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 back in 2009. Since then, researchers have created mini versions – called organoids – of the liver, pancreas, bladder and more. They even moved from mammals to reptiles, successfully growing snake venom glands. Last year, Clevers’s PhD students elected to work on human tear glands.
After first 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 broke it up into small pieces and fed it some more to create several mini-glands. “They looked like little balloons,” said Clevers.
Tear glands are useful to their human host in a plethora of ways. They produce a thin layer of liquid that sheaths the cornea, lubricating the surface of the eye, protecting it from irritants and infections, and supplying nutrients. The glands are also responsible for manufacturing tears, whether due to physical provocation, say somebody sticks a nail in your eye, or emotional angst, caused by, for instance, a car that runs over your pet cat. In either case, the brain instructs the tear glands to weep.
“The chemical message that comes from the neurons … to your tear glands is adrenaline. So, to really show that we had functional tear glands, we needed to show that they would respond to adrenaline,” said Clevers.
When the mini-organs were given a persistent supply of the growth factor cocktail, they didn’t produce much tear fluid upon encountering adrenaline. But once they were cut off from the juice, the cells stopped dividing and were allowed to settle down and mature – the adrenaline quickly produced tears, he explained.
The little balloon-like glands rapidly got swollen because there were no ducts for the liquid to escape. Eventually, they were made to rupture or ruptured themselves, dribbling out some liquid in the form of droplets, added Clevers.
The model has some limitations. The researchers captured one cell – the ductal cell – that the tear gland is composed of, but the glands also comprise other cells. In addition, these organoids are not part of the human body – in which tear glands could be wrapped around by muscle and blood vessels – so there are limitations to their functioning, he cautioned.
“It is a reductionist model. But the essence of the tear gland is captured: namely, the tear formation and then the adrenaline-induced production of tear droplets.”
This model can now be used by researchers globally to identify new drugs for patients who do not produce enough tears and to study how cancers of the tear gland form and may be treated. Eventually, this type of organoid may even be transplantable to patients with non-functioning tear glands, the authors suggested in the journal Cell Stem Cell.
Meanwhile, researchers in Clevers’s lab already have their eye on their next project: crocodile tears.
“We want to grow crocodile tear glands,” said Clevers. “Crocodiles don’t cry because they’re sad or something; they’re 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.”