Scientists Create Immortalized Human Lip Cell Model

Human lips play numerous roles, from assisting in speech and eating to signaling emotions and health. However, the skin on our lips has a distinct structure and function compared to other skin on the body, making lip conditions complex to treat. Despite the need for research, lip-specific cells are difficult to source, and models to study lip biology have been limited. Recently, scientists developed a continuously replicating model of human lip cells from donated tissue, which may advance the understanding of lip biology and improve treatments for conditions such as cleft lips.

Unique challenges in lip research

Lip cells differ significantly from other skin cells, and models using primary lip cells have been hard to sustain in the lab. Primary cells, directly taken from an individual’s tissue, closely resemble their original counterparts but have a limited lifespan, which can be a barrier to research. Additionally, human lip tissue is rare, as it’s usually only available from individuals undergoing surgery, making it both difficult and expensive to obtain.

Researchers have often sought immortalized cells that can replicate indefinitely. Immortalization involves modifying cells so they continue reproducing when they would typically stop. For this model, scientists adapted donated cells from patients who underwent surgery for a lip laceration or cleft lip.

“The lip is a very prominent feature of our face. Any defects in this tissue can be highly disfiguring. But until now, human lip cell models for developing treatments were lacking."

Dr Martin Degen

Creating the model: immortalization of lip cells

To produce this lip cell model, the scientists used a retroviral vector to modify the cells’ genes, ensuring that they could bypass the usual cellular lifespan limit. By altering the length of telomeres – the protective caps on chromosomes that typically shorten as cells replicate – they were able to extend the cells' longevity. These adjustments enabled the lip cells to reproduce in the lab without the risks that often come with cellular immortality, such as changes that can resemble cancerous growth.

After modification, the new cell lines underwent a series of tests to confirm that they remained genetically stable and closely mirrored primary lip cells. The scientists verified that the immortalized cells did not develop cancer-like properties by examining chromosomal stability and testing growth on soft agar –a medium on which only cancer cells should grow. These tests showed no abnormalities, indicating the cell lines maintained the essential characteristics of the original tissue.

Potential applications: wound healing and infection models

The research team then explored potential uses for these cells by examining how they might function in models of wound healing and infection. When scratched, untreated lip cell samples closed their “wounds” within about eight hours, while cells treated with growth factors healed more rapidly, similar to skin cells from other body areas. These results suggest that immortalized lip cells can simulate real healing processes, potentially making them useful for studies on lip repair.

To evaluate their response to infection, the team introduced Candida albicans – a yeast associated with infections in immune-compromised patients and those with cleft lips – into a 3D lip cell model. As expected, the pathogen effectively invaded the lip cell model, resembling its behavior in natural lip tissue. These findings indicate that this lab model could be used to study various aspects of lip health and disease, including responses to infections.

Future directions in lip cell research

This new model presents a valuable tool for researchers aiming to understand genetic and cellular mechanisms underlying lip conditions. For instance, the team noted that lip keratinocytes – the cells forming the protective layer of skin on the lips – can vary between labial skin and mucosal cells. Since different research areas may require specific cell types, scientists have developed methods to characterize and purify these cells accordingly, further enhancing the model’s adaptability.

With further research, this model could serve as a foundation for developing clinical treatments and conducting in-depth studies on lip-related health issues, paving the way for improved interventions for patients with challenging lip conditions.

Reference: Mansour F, Parisi L, Rihs S, et al. Immortalization of patient-derived lip cells for establishing 3D lip models. Front Cell Dev Biol. 2024;12:1449224. doi: 10.3389/fcell.2024.1449224

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