Science & Technology: BIOTECH
THE LATEST FROM THE LABS: HUMAN SKIN
The FDA is about to approve commercial use of living tissue grown by two biotech outfits
In antiseptic rooms in Massachusetts and California, workers swathed in germ-free suits are carefully watching over high-tech tubs containing dissolvable proteins. Into these tubs, the workers add skin cells harvested from the foreskins of circumcised newborns. The cells are fed with nutrients and growth factors so they grow and multiply. After about three weeks, if all goes well, the workers can toast what they have created: living human skin--sheets of it that can be picked up, cut into pieces, and grafted onto victims of burns and chronic wounds. "It's a fantastic process," says Dr. C. Keith Bowering, a dermatologist at Royal Alexandra Hospital in Edmonton, Alberta, who has treated 12 patients with a lab-grown skin after conventional treatment failed to heal their chronic wounds.LIVERS, TOO? Dr. Jeffrey C. Page, executive dean of the California College of Podiatric Medicine in San Francisco, says he has high hopes that engineered skin will eventually be used to treat an array of chronic wounds. But "the most exciting consequence will likely be for burn treatments." For Nellie E. Sullivan, a 51-year-old diabetic in Allentown, Pa., engineered skin was the only treatment that worked on a painful sore on the ball of her foot that had not healed in over a year. "I'm well pleased," she says. "I was afraid I was going to lose my leg." After seven weeks of treatment, she says, there isn't even a dent where the wound was.
So far, in the U.S., engineered skin has been available only for clinical trials. But the Food & Drug Administration is expected to approve it for commercial use during the next few weeks. Two companies are independently seeking approval: Organogenesis Inc. of Canton, Mass., and Advanced Tissue Sciences Inc. of La Jolla, Calif. The two companies' skins were approved in Canada last August, and in January an FDA advisory panel recommended that they be cleared for marketing here.
Engineered skin could be a godsend to the 4 million people who suffer from chronic skin ulcers and the 100,000 burn victims admitted to hospitals each year in the U.S. Right now there are few good options when a wound is unable to heal itself. Some temporary artificial skin replacements are available, or skin can be temporarily grafted from a cadaver. But these products are expensive, often don't take, and in the case of cadaver skin, there is always a danger that a virus or disease will be transmitted as well. Alternatively, the patient's own skin can be grafted after being surgically removed from another part of the body--a painful, risky procedure.
The engineered skins are the first of an entire bionic body's worth of laboratory-grown tissues that researchers are working on, including cartilage, nerves, blood vessels, and even livers and pancreases. Such organs could help save the lives of many of the 100,000 Americans who die each year while waiting for an organ transplant. It will likely be at least 15 years before a fully transplantable organ, such as a liver, is available, cautions Dr. Peter C. Johnson, president of the Pittsburgh Tissue Engineering Initiative at the University of Pittsburgh. "But the skin is an important first step," he says. "Now you'll see the technology accelerate. This is like the beginnings of the space program."
Just don't call these products artificial skin. Organogenesis' Apligraf and Advanced Tissue's Dermagraft look, feel, and act just like a patient's natural skin. Because the body's immune system doesn't reject skin cells, the engineered skin is quickly incorporated into the body. Once grafted on, the skin sends out growth factors and tissue proteins that promote healing and encourage the patient's natural skin to grow toward it. Clinical studies suggest that after three months, it's almost impossible to tell where the engineered skin stops and the patient's own begins.
The concept behind these skins was pioneered 15 years ago by Robert S. Langer, a professor at Massachusetts Institute of Technology, and Dr. Jay Vacanti of Boston Children's Hospital. They discovered that certain proteins could act as scaffolds on which living cells would grow.HARD TASK. Both Organogenesis and Advanced Tissue have spent some 10 years developing universal skin substitutes that can be applied on an outpatient basis. That's no easy task, considering the complexity of skin. The epidermis, the outermost layer that forms a waterproof coating for the body, is as thin as a piece of paper but has four or five sublayers. Next comes the dermis, only slightly thicker than the epidermis and primarily made up of connective tissue cells called fibroblasts.
Organogenesis's Apligraf and Advanced Tissue's Dermagraft each start with a baby's foreskin, a consistent, readily available source. Plus, young skin grows better. One piece of foreskin can produce four acres of engineered skin with a five-day shelf life. But from there, the two products differ significantly. The biggest difference: Dermagraft recreates only the dermis layer, while Apligraf consists of both the epidermis and dermis.
Medical experts say the epidermis provides important functions but they are uncertain whether it is necessary for a skin graft. "You get more of the normal barrier of the skin, but the epidermis might also send out signals that healing is already complete," says Dr. William H. Eaglstein, chairman of the Department of Dermatology at the University of Miami Medical School. "But as a practical matter, no one really knows which [Apligraf or Dermagraft] is better. They haven't been tested against each other."
Advanced Tissue's Dermagraft, which has been licensed to Smith & Nephew, a British health-care company, is awaiting approval in the U.S. for diabetic foot ulcers. About 800,000 diabetics develop these persistent sores each year, according to the American Diabetes Assn. In studies presented to the FDA, almost 60% of patients who received one piece of Dermagraft a week for eight weeks were completely healed after 12 weeks, compared with 32% of patients receiving conventional treatments.
Advanced Tissue Sciences suffered a setback in March, when the FDA requested more data and found some problems with the company's manufacturing process. That could delay approval, says David S. Weber, an analyst at SBC Warburg Dillon Read, "but there's no reason to think that they won't get it."
Organogenesis' Apligraf, licensed to Novartis, is awaiting FDA approval for venous leg ulcers, chronic wounds that affect about 600,000 patients in the U.S. each year and frequently lead to death. The standard treatment now is compression bandages, the same method used 100 years ago. In a study published in the March issue of the Archives of Dermatology, five applications of Apligraf over three weeks cut the median time for wound healing by two-thirds, to 61 days, compared with 181 using bandages. Apligraf "represents a significant advance in the treatment of venous ulcers," says Dr. Vincent Falanga of the University of Miami Medical School, the lead researcher on the study.
The potential market for the treatment of leg and foot ulcers is about $1 billion each, analysts estimate. That kind of opportunity boosted the stocks of both companies after the FDA advisory panel recommendation in January. (Advanced Tissue declined sharply after the FDA warning about its manufacturing process in late March.) Patients willing to pay the price could even use bioengineered skin for cosmetic purposes, says Page of the California College of Podiatric Medicine. The bionic body as fountain of youth? Maybe. But the most important use of the skins will be to save lives.By Catherine Arnst in New YorkReturn to top