Scientists experimenting with clusters of lab-grown stem cells designed to mimic human tear glands successfully made them cry, reports Heidi Ledford for Nature. These cell clusters, or organoids, might one day be able to be transplanted into the eyes of real people, where they could remedy dry eye diseases such as the autoimmune condition known as Sjögren’s syndrome.
Though those of us fortunate enough to have working tear glands don’t spend much time thinking about them, the liquid they produce provides essential lubrication to the eye and contains proteins and other compounds that stave off infections and provide our peepers with nutrients.
"What struck us is that at least 5 percent of the adult population is estimated to have dry-eye disease, which is most of the time related to a defect of tear production by the tear gland," says Yorick Post, a biologist at the Hubrecht Institute and the paper’s co-first author, in a statement. "But treatment options are limited because there was no complete understanding of the biology and no reliable, long-term in vitro model to study the tear gland."
The researchers created the miniaturized tear organoids in petri dishes by isolating cells from healthy tear glands and supplying them with a steady stream of a protein-rich solution called growth factors, reports Karina Shah for New Scientist. The team reports their findings in a new paper published in the journal Cell Stem Cell this week.
“Adult stem cells are already specialized and they know what to make – we just have to encourage them with growth factors,” Hans Clevers, a developmental biologist at the Hubrecht Institute in the Netherlands and the study’s senior author, tells New Scientist. “This happens within a matter of two or three days: you see small cystic structures appearing that grow into the organoids.”
To show that the mini-tear glands grown in the lab would function the way real ones do, the researchers had to show that they would cry when presented with the right neurochemical signals.
“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,” Clevers tells Natalie Grover of the Guardian.
But when the organoids were on their steady diet of growth factor-laden solutions, they didn’t do much crying when presented with adrenaline, according to the Guardian. Once the researchers turned off the growth factor drip, Clevers tells the Guardian, the organoid cells stopped dividing, matured and quickly responded to the introduction of adrenaline by weeping in their respective petri dishes.
However, per Nature, the organoids in the experiments lacked ducts to let the fluid escape, so their crying looked more like inflating water balloons. Promisingly, when the team transplanted the organoids into mice, the cells developed duct-like structures, according to Nature.
If the same holds in human subjects, the team’s findings could produce a host of new therapies for people suffering from dry eyes.
Clevers’ group has also used stem cells to grow organoid glands that produce snake venom, and hope to use their expertise to create tear gland organoids for reptiles.
“We are actually hoping to grow crocodile tear glands,” Clevers tells New Scientist. “We already know we can do it with reptiles, and it likely looks like it could be possible with crocodiles too.”