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HPV Researchers at NIAID Find Way To Immortalize Skin Cells

photo of a researcher examining an agar plate
A researcher examines an agar plate.
Credit: NIH
Cancer-causing strains of human papillomavirus (HPV) are well known, but there are also types of HPV that, while not cancer-associated, may still cause genital warts. Non-cancer-causing HPV types are difficult to study because they are hard to grow in skin cells. A new technique pioneered by NIAID doctoral student Sandra Chapman and Principal Investigator Alison McBride, Ph.D., and their colleagues may soon be helpful in studying both cancer-causing and non-cancer-causing strains of HPV.


Immortalizing Tough-to-Grow Cell Lines

HPV and other papillomaviruses can persist for years in the body’s skin cells. In culture dishes, however, human skin cells grow slowly and stop dividing after about 20 cell divisions, making it difficult to study HPV. In a 2010 study published in the Journal of Clinical Investigation, the investigators described a new method to immortalize human skin cell lines, that is, make it possible for them to continue dividing indefinitely. “We anticipate that [these skin cells] will be invaluable for research and may have significant therapeutic and diagnostic potential,” says Dr. McBride.

Past research by other investigators had suggested a role for drugs known as ROCK inhibitors in regulating skin cell division. McBride’s study team added a ROCK inhibitor called Y-27632 to skin cells to see if it would help HPV grow in these cells, and found that it allowed skin cells to continue dividing beyond the 20 divisions.

“We were surprised to find that these cells were healthier and grew faster than normal cells,” says Dr. McBride. Also surprisingly, the cells grown in the presence of Y-27632 did not have the genetic damage or unusual appearance that cells from similar experiments often had.

“They were so healthy and robust that we wanted to follow their story as they continued dividing,” Dr. McBride continues. “[The cells] ended up becoming immortalized.”

The HPV Connection and Possibilities Beyond Papillomaviruses

The researchers found parallels between the immortalized cells and cells infected by HPV 18, a strain that has been linked to cervical cancer. Unlike HPV 18-infected cells, however, the immortalized cells still had working anti-cancer genes and were able to grow and behave normally. The similarities suggest that these skin cells could be useful in studying HPV.

In addition, the cell proliferation method could be used in gene therapy by introducing therapeutic genes into skin cells in the lab, having them grow and divide, and regrafting the cells onto the patient’s skin. For example, the study authors explain, it may be possible to take skin or tissue from a patient and grow it in the lab, then use the cells to test treatments tailored to the individual’s specific condition or disease. The ability to grow patient-specific skin cells and tissues could help to treat burn victims as well. “Being able to amplify cells from a simple skin biopsy has research and therapeutic benefits way beyond the papillomaviruses,” says Dr. McBride.

The investigators have already found similar results using skin cells from different parts of the body and from different animals. Their next steps include creating a skin graft of these cells in animal studies to make sure they function normally. The researchers also plan to study drugs similar to Y-27632 and to find out exactly how they immortalize cells.

Last Updated June 23, 2010