Harvard Doctors Reproduce Skin Cells for Grafting

Human cells of various types have long been successfully studied in laboratory petri dishes. Now, with the help of research performed at a Harvard Medical School teaching hospital, doctors can remove skin cells from a patient, culture them to create a new sheet of skin, and graft them back onto the patient to heal wounds.

"This is the first situation that cells have been taken out of someone and put back onto that person," says G. Gregory Gallico, assistant clinical professor of surgery at the Medical School and a plastic surgeon at the Massachusetts General Hospital (MGH). "It's a quantum leap."

Gallico says that the technique is being used all around the world, from Johns Hopkins Medical School in Baltimore, Md., to Shriners Burn Institutes in Galveston, Tx. and Cincinnati, Oh., to Hanover, Germany.

While most cells can be grown in culture, it is often difficult to recreate a reasonable facsimile of the original organ. In the technique, known as autografting, doctors can now remove a group of skin cells one centimeter square from behind a patient's ear, or from a patient's stomach, and within three weeks reproduce a sheet of the cells of whatever size is necessary to treat the patient.

Research with skin cell cultures was first reported in 1975, when a paper by two MIT scientists, Howard A. Green, now a clinical fellow in dermatology at the Medical School, and James G. Rheinwald, now a biochemistry tutor, announced that they had successfully grown skin cells in culture.

Clinical use of cultured skin cells began in 1982, when Gallico and colleague Nicholas E. O'Connor, instructor in surgery at the Medical School and a surgeon at the Harvard-affiliated Brigham and Women's Hospital, first used the technique to treat a massively burned patient at the Shriners Burn Institute in Boston.

In addition to their use in the treatment of burn victims, the cultures are utilized today to treat skin cancer patients as well as victims of other dermatological diseases.

Jessica L. Fewkes, assistant professor of dermatology at the Medical School and co-director of the MGH dermatologic surgery unit, is using autografts to replace patient skin loss during surgery.

Fewkes, a skin oncologist, utilizes the technique in skin cancer and leg ulcer surgery. Removal of skin cancers often creates large holes in the epidermis, or outermost layer of skin, which must be filled in, she says. The treatment of leg ulcers, large skin wounds which do not heal, is based on skin replacement.

"What's nice about [autografts] is that there's no anesthesia, no sewing," she says. "For the patient, it's relatively painless."

Autografting Versus Conventional Methods

Fewkes also says that the surgery only takes about 15 minutes, and that for all these reasons, autografting is a big improvement over conventional grafting.

In conventional techniques, known as split thickness skin grafting, doctors replant both the epidermis and the underlying layers of skin with skin from another part of the body.

Split skin grafting is currently the method of choice for most physicians, and a 1990 study by Gallico, O'Connor and John P. Remensnyder Jr., associate professor of surgery at the Medical School and director of the MGH operating rooms, found that the method produced an 84 percent success rate among severe burn victims, while autografting produced a 68 percent success rate.

With severe burn cases and patients who might have skin cancer as well as another skin ailment such as psoriasis, Fewkes says that autografting presents an advantage over split thickness grafting.

Once created, an autograft can be kept frozen and used to generate more sheets of skin whenever needed. For these patients, who may have a limited amount of skin from which to proceed with split skin grafting, autografting may be the only way to heal skin wounds.

Such a bank of cell cultures is now available at BioSurface Technology, a Cambridge company formed by Green in 1986. Doctors who use the technique can now send epidermal cells to BioSurface and receive complete cultures within three weeks, rather than be forced to maintain their own cell culture laboratories, an expensive and time consuming task.

The Next Step

Gallico said that the next step in researching cultured skin cells is the possibility of using cells from one person to treat another, a process known as allografting. Allografts would make it possible to use cultured skin cells at all times, since a bank of cultures could be kept at any surgical center for immediate use.

"Allografts would make things much easier," says Gallico. "Right now, there's a three-week span in which we can't do anything."

The problem, says the surgeon, is that cells from one person would be rejected by the immune system of the other. Another complication, he says, is that skin donated by others might contain viruses such as HIV, which causes AIDS.

Fewkes says that researchers are investigating the possibility of using cultured epithelial cells from neonatal foreskins as an experimental dressing for leg ulcers. Scientists are also examining ways to create synthetic epidermis, based on current knowledge learned from culturing skin cells.

Gallico says that the autografts can be used as a "living laboratory" while they are being grown. Previously, researchers had used cultures to study cell physiology, and this research is continuing.

Studies may also provide clues about patterns of growth and differentiation in skin cells. A 1989 study by Carolyn C. Compton, associate professor of pathology at the Medical School and a pathologist at MGH, found that the skin of patients treated with cultured skin grafts up to five years ago had developed lower layer skin, or dermis, rather than developing scar tissue.

"The cells are evidently getting messages from the areas on which they are placed," says Gallico.