Laboratory-Produced Human Skin, Researchers Say, Is Only the Beginning
In the latest life-imitates-art development from the biotechnology industry, a La Jolla company has begun selling organic human body parts.
The first product from Advanced Tissue Sciences is skin grown in a laboratory from a baby’s foreskin. At $400 for a 2-by-3-inch piece, it’s expensive. But it’s worth every penny if you’re suffering from severe burns or if you’re suffering from a diabetic foot ulcer that won’t heal and could require amputation.
And other human spare parts are in development in laboratories across the country, including cartilage, bone, blood vessels and heart components.
“With this technology, there is no reason why we can’t grow any part of the body,” says ATS Chief Operating Officer Gail Naughton, who founded the company in 1987 and took it public a year later. Naughton is a pioneer in the field of tissue engineering, whereby scientists combine living cells, organic chemicals and various synthetic materials to grow human body parts for transplant.
ATS’ first product, a skin for burns, hit the market this spring. Dermagraft, for treating diabetic foot ulcers, is available in Canada and Britain and is under expedited review by the Food and Drug Administration.
Wall Street has high hopes, valuing the company at nearly $500 million even though it had just $3.3 million in revenue for its most recent quarter.
The process of growing skin begins with a living “seed” cell: One neonatal foreskin, for example, could yield 5 million skin implants, Naughton says. (So far, ATS is the only company to commercialize a fully human-based engineered tissue product. Rival firms use animal cells as seeds.)
In ATS’ process, cells are placed in a three-dimensional mesh “scaffold” and stored in a carefully monitored enclosure designed to simulate the human body. The incubator feeds the cells with oxygen, vitamins, amino acids and other nutrients while removing waste products.
“The tissue grows in the very controlled environment, which is basically an artificial womb,” Naughton explains.
Two weeks later, the dissolvable scaffold with the new tissue is ready to be placed over the wound or implanted in the body. Rejection by the body’s immune system is less of a problem with tissue engineering than with traditional transplants: If the original cell came from the patient, the body does not recognize the new tissue as foreign, and a layer of Dermagraft skin does not trigger immune-system defenses at all.
According to Naughton, ATS’ patented technique can be applied to other tissues as well. ATS funds research on lab-grown heart valves and blood vessels, which could eventually eliminate the need to remove arteries from a patient’s leg for a heart-bypass operation.
But don’t expect hearts on demand any time soon. Most likely to follow skin as the second engineered body component to enter the FDA approval process is cartilage. ATS and other laboratories intend to use engineered cartilage to repair damaged joints such as knees, for which plastic replacements are used now.
Charlotte, N.C.-based Reprogenesis, a company founded in 1993 with technology licensed from the Massachusetts Institute of Technology and Children’s Hospital in Boston, is putting home-grown cartilage to the test in clinical trials to treat incontinence in adults and a pediatric disorder that causes urine to back up.
Reprogenesis also funded an experiment this summer in which researchers at Children’s Hospital successfully repaired a gap in the urinary bladder of a baby lamb using tissue grown from its own cells.
But growing from scratch what are known as the “functional” organs--hearts, lungs and kidneys, for example--is a far more complex task than designing organ or tissue “patches.”
“People remember cutting off a starfish’s arm in the fourth grade and it grows back,” Naughton says. “They wonder why we can’t do that.”
Kidneys and livers, for example, are not only composed of many kinds of cells, they also require a complex system of blood vessels difficult to grow on a scaffold.
“With skin or cartilage, if it’s not the substance you’re trying to achieve, it can still fill a void. But with functional organs, you have to leap a higher hurdle or it just won’t work,” says Robert Langer, professor of chemical and biomedical engineering at MIT.
But according to Joseph Vacanti, a professor of surgery at Harvard Medical School, the similarities between functional and structural tissue outnumber the differences.
“One can build from the understanding of how to grow non-vital organs and progress to vital organs,” he says.
The two scientists envision a process revolving around the slow release of growth factors such as hormones that would prompt the creation and movement of blood vessel cells at the appropriate time. The growth factors could be stored inside the scaffolding or in time-release microspheres positioned near the scaffolding.
It was Vacanti and Langer’s research that led to Vacanti’s brother and a colleague implanting an engineered human ear into the back of a mouse last year, a well-publicized experiment funded by ATS.
But don’t dare refer to Vacanti as Dr. Frankenstein.
“We have no intent to build a person or a brain or anything like that,” he says. “With non-vital organs, we’re trying to improve the quality of life of people, and with vital organs we’ll try to solve the organ scarcity.”
And that won’t come a moment too soon for the people who need organ transplants. According to the United Network for Organ Sharing, each year 4,000 people in the United States die waiting for a transplant; 100,000 more die without even qualifying for the waiting list. Even in a best-possible scenario, with every suitable donor available, the organ supply would not meet that demand, experts say.
There are several other biotech-based efforts underway to develop fully functional implantable organs. In October, researchers at Bath University in England reported the successful cloning of headless frog embryos to create an “organ sack” of usable tissue. However, human applications are many years away.
Meanwhile, research into “trans-genic” pigs, whose organs can be transplanted into humans without rejection, is surrounded with controversy because of fears of “mad cow” disease and animal viruses.
Ultimately, though, some or all of these techniques are expected to help solve the organ shortage.
“Surgeons are simply limited by not having enough organs to put in,” Naughton says. “And that’s what keeps us going--walking into transplant centers and seeing that.”
*
David Pescovitz (pesco@well.com) is the co-author of “Reality Check” (HardWired, 1996) and a contributing editor at Wired magazine.
