World-first 3D cell model to help develop treatments for devastating lip injuries

A continuously replicating model of lip cells.

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Lips play vital physiological roles and are essential to perceptions of health and beauty. Injuries, abnormalities, or congenital issues like cleft lip require careful attention to restore function and appearance. A deeper understanding of lip anatomy and biology is essential. Still, the absence of clinically relevant human lip cells and effective three-dimensional lip models hinders research progress in this field.

Researchers have successfully created a continuously replicating model of lip cells using donated lip tissue. These cell lines can be grown indefinitely, enabling the development of 3D models that advance research in lip biology and facilitate testing for repairs of conditions like cleft lips.

This breakthrough represents a significant step in studying lip function and treatment options.

Dr Martin Degen of the University of Bern said, “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.”

Researchers obtained skin cells from two patients—one with a lip laceration and another with a cleft lip—to create new, continuously replicating lip cell lines. They used a retroviral vector to deactivate a gene that limits cell lifespan and modified telomeres to enhance longevity.

The cell lines underwent rigorous testing to ensure genetic stability and retained characteristics of primary cells. To confirm they did not develop cancer-like traits, the scientists checked for chromosomal abnormalities and tested growth in soft agar (where only cancer cells can grow).

The new cell lines showed no chromosomal issues and did not proliferate in the agar. Additionally, they demonstrated protein and mRNA production similar to those of their unmodified counterparts.

The scientists tested the new lip cell lines as potential models for studying lip healing and infections. They simulated wound healing by scratching the cell samples and observed that untreated cells closed the wound in eight hours, while those treated with growth factors healed even faster, consistent with results from skin cells in other areas of the body.

Next, they created 3D models using the cells and infected them with *Candida albicans*. This yeast can lead to severe infections, particularly in individuals with compromised immune systems or cleft lips. The cells behaved as expected, with the pathogen rapidly invading the model, mimicking how it would affect actual lip tissue.

Degen said, “Our laboratory focuses on better understanding the genetic and cellular pathways involved in cleft lip and palate. 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. 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.”

Journal Reference:

  1. Farah Mansour, Ludovica Parisi et al. Immortalization of patient-derived lip cells for establishing 3D lip models. Frontiers in Cell and Developmental Biology. DOI: 10.3389/fcell.2024.1449224
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