Press release Hubrecht Institute

Crying human tearglands grown in the lab

16 March 2021

Researchers from the lab of Hans Clevers(Hubrecht Institute)and the UMC Utrecht used organoid technology to grow miniature human tear glands that actually cry. The organoids serve as a model to study how certain cells in the human tear gland produce tearsor fail todo so.

Scientists everywhere can use the model to identify new treatment options for patients with tear gland disorders, such as dry eye disease. Hopefullyin the future, the organoidscan even be transplanted into patients with non-functioning tear glands. The results will bepublished in Cell Stem Cell onthe16thof March.

The tear gland is located in the upper part of the eye socket. It secretes tear fluid, which is essential for lubrication and nutritionof the corneaandhas antibacterial components. Rachel Kalmann(UMCU), ophthalmologist and researcher on the project, explains: “Dysfunction of the tear gland, for example in Sjögren’s syndrome, can have serious consequencesincluding dryness of the eye or even ulceration of the cornea. This can, in severecases, lead to blindness.” However, the exact biology behind the functioning of the tear gland was unknown and a reliable model to study it was lacking. That is, until now: researchers from the group of Hans Clevers (Hubrecht Institute)present the first human modelto study how the cells in the tear gland cry and what can go wrong.

Crying organoids

Theresearchersused organoid technology to grow miniature versions of the mouse and human tear gland in a dish. These so-called organoids are tiny 3D-structures that mimic the function of actual organs. After they cultivated these tear gland organoids, the challenge was to get them to cry. Marie Bannier-Hélaouët, researcher on the project, explains: “Organoids are grown using a cocktail of growth-stimulating factors. Wehad to modify the usual cocktail to make theorganoidscapable of crying.Once the researchers found the right mixture of growth factors, they could induce theorganoids to cry. “Our eyes are always wet, as are the tear glands in a dish,” Bannier-Hélaouëtsays.

Swelling uplike a balloon

Similar to the way people cry in response to for example pain, the organoids cry in response to chemical stimuli such as noradrenaline. The cells of the organoids shed their tears on the inside of the organoid, which iscalled the lumen. As a result, the organoid will swelluplike a balloon. The size of the organoidscan therefore be used as an indicator of tear productionand-secretion. “Further experiments revealed that different cells in the tear gland make different components of tears. And these cells respond differently to tear-inducing stimuli,” says Yorick Post, anotherresearcher on the project.

Atlas of cells

The tear gland is composed of several cell types, but the current model only captures one, the ductal cell. In their paper, the researchers present an atlas of the cells in the tear gland to demonstrate their differences. They generatedthis atlas using single-cell sequencing; a method with which individual cells can be examined and characterized. Post explains: “In the future, we would like to also grow the other tear gland cell type, so-called acinar cell,in a dish. That way, we can eventually grow a full tear glandin the lab.” With theatlas, the researchers were also able to identify new tear products, which help protect the eye from infections.

Transplanting organoids

The development of the miniature tear glands holds promise for patients suffering from tear gland disorders. Scientists everywhere can use the model to identify new drugs for patients who do not produce enough tears. Additionally, the organoids can be used to study how cancers of the tear gland formand may be treated. “And hopefully inthe future, this type of organoids may even be transplantable to patients with non-functioning tear glands,” Bannier-Hélaouëtconcludes. The study demonstrates once more the broadpotential of organoid technology for science and medicine.

Hubrecht Institute

The Hubrecht Institute is a research institute focusing on developmental and stem cell biology. It encompasses 24 research groups that perform fundamental and multidisciplinary research, both in healthy systems and disease models. The Hubrecht Institute is a research institute of the Royal Netherlands Academy of Arts and Sciences (KNAW)., located on the Utrecht Science Park ‘De Uithof’. Since 2008, the institute has been affiliated with the University Medical Center Utrecht, advancing the translation of research into clinical practice. The Hubrecht Institute has a partnership with the European Molecular Biology Laboratory (EMBL). 

The Hubrecht Institute is located in Utrecht (Uppsalalaan 8, 3584 CT Utrecht).

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