Lip skin is different from the rest of our skin, and lip cells are hard to grow in the lab and difficult to acquire from donors, which has been a hurdle for research into treatments for lip-related conditions. Scientists have now developed a way to grow continuously replicating lip cells on a dish in the laboratory, and the results offer new opportunities for lip biology research as well as experimenting with treatments for conditions like cleft lips.

If there’s part of the body you probably take for granted, it’s probably your lips. These fleshy appendages serve so many important functions for humans that it’s easy to lose track of them: they not only help us eat and drink and communicate (both with words and our facial expressions), but they also serve as symbols of health and beauty. Such versatility requires a complex structure, which is where the problem lies for scientists trying to grow lip cells for research.

“The lip is a very prominent feature of our face,” Dr Martin Degen of the University of Bern explained in a statement. “Any defects in this tissue can be highly disfiguring. But until now, human lip cell models for developing treatments were lacking. With our strong collaboration with the University Clinic for Pediatric Surgery, Bern University Hospital, we were able to change that, using lip tissue that would have been discarded otherwise.”

Primary cells are derived directly from a donor’s tissue, which means they are an excellent model system for researching physiology and biochemical processes in humans. However, they can be difficult (and expensive) to obtain and maintain. They also have a limited lifespan and eventually stop dividing, which means they cannot be reproduced indefinitely.  

But if you can’t acquire primary cells easily, what can you do? One option is to immortalize the cells so they can be grown in a laboratory. This can be done by changing the expression of certain genes, which enables the cells to continue reproducing even after they would normally reach the end of their life cycle.

However, as the researchers note in the paper, the accessibility of immortalized keratinocytes (major cells of the epidermis) has been restricted and only used on certain tissues, such as the foreskin, the lungs, the gingiva, and the floor of the mouth. This is what makes the work of Degen and colleagues so important; they have pioneered a process to immortalize lip cells.

“To the best of our knowledge”, the team explains in their study, “this marks the first instance of the introduction of such cells into the scientific community, which represents an important step toward a better understanding of lip-related diseases and malformations.”

The team took skin cells from tissue donated by two patients: one who was undergoing treatment for a lip injury and one who was being treated for a cleft lip. Using a retroviral vector (a modified virus that delivers genes into cells), the team was able to deactivate a gene that stops cells’ life cycles while also changing the length of their telomeres: regions at the end of chromosomes that protect them and dictate the cell’s lifespan. This improved the lip cells’ overall longevity.

Following this, the team tested the new cell lines to check the genetic code was still stable so they could replicate and retain the desired characteristics of the primary cells. The team also examined the cell lines for any chromosomal abnormalities that could represent cancer-like characteristics. They tried to grow the new lines and a line of cancer cells on agar gel – this is because cancer cells should be the only cells that grew on that medium.

The new cell lines did not exhibit any chromosomal abnormalities, and they did not grow on the agar gel. In addition, the team confirmed the cell lines behaved like their primary cell counterparts, which they checked by testing their protein and mRNA production.

With this done, the team moved on to testing how the cells could perform as a potential experimental model for lip healing and other treatments. For instance, the researchers scratched samples to check whether the cells could work for wound healing research. Under normal conditions, untreated cells close wounds after around eight hours – but the treated cells close wounds faster than this. The researchers found that the new lip cells matched those of cells taken from elsewhere in the body.

Finally, the scientists infected 3D models of the cells with a yeast, Candida albicans, which can cause a serious infection for people with weak immune systems or cleft lips. The infection invaded the model as it would real lip tissue.

“Our laboratory focuses on obtaining a better knowledge of the genetic and cellular pathways involved in cleft lip and palate,” Degen added. “However, we are convinced that 3D models established from healthy immortalized lip cells have the potential to be very useful in many other fields of medicine.”

“One challenge is that lip keratinocytes can be of labial skin, mucosal, or mixed character,” he added. “Depending on the research question, a particular cell identity might be required. But we have the tools to characterize or purify these individual populations in vitro.”

The results may offer an opportunity for researchers to enhance our understanding of complexities involved in lip biology and disease, and may be valuable in fields as diverse as skincare, dentistry, and the treatment of conditions such as cleft lips.

The paper is published in the journal Frontiers.