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Scientists Grow Human Corneas in Lab

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TIMES MEDICAL WRITER

Scientists have grown nearly complete human corneas in a laboratory dish for the first time, fashioning a possible new tool to replace animals in some product safety testing and advancing toward an abundant future supply of vital tissue to help restore sight in people.

The scientists say the bioengineered tissue has many key properties of a real human cornea, the pupil’s transparent covering. The lab-made tissue is clear, consists of the same three-layered sandwich of living cells, and appears to respond to some chemicals much as real corneas do, according to a report published today in the journal Science.

Further research is necessary to determine whether the experimental material can be used in product tests or human cornea transplants, which number about 46,000 a year. But if it pans out, the first application will probably be in reducing the estimated 100,000 animals used in eye safety testing annually, experts said Thursday.

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“It’s a major advance,” said Alan Goldberg, director of the Center for Alternatives to Animal Testing at the Johns Hopkins School of Public Health, who reviewed the report. “But now the hard work begins,” he said of the need for others to replicate the work.

The scientists, based in Canada and the United States, received $300,000 in partial funding over four years from Procter & Gamble, the personal care and drug company. Animal protection advocates, who have harshly criticized the company for its widespread use of animals to screen products, hailed the new research Thursday.

“This is really exciting,” said Mary Beth Sweetland, a vice president of People for the Ethical Treatment of Animals, which has led protests against the company and encouraged product boycotts. “With every little step Procter & Gamble takes . . . we say, ‘Way to go.’ ”

Procter & Gamble toxicology expert Rosemarie Osborne, a co-author of the study, said: “This is one step in developing valid, useful, non-animal test methods to protect the safety of consumers.”

A coordinated attempt to validate the engineered cornea material as a toxicology screen is underway at three laboratories: Procter & Gamble; Unilever, the personal care company; and the Institute for In Vitro Sciences, which seeks to reduce or replace animals in product safety screening.

The most notorious product safety eye screening, the so-called Draize test, involves placing a compound or chemical directly in a rabbit’s eye and documenting any irritation. Soaps, shampoos, drugs, toothpaste and other personal care products are screened that way, and so are chemicals that go into paints and other environmental products.

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Such screening is not always required by the government. Companies often conduct the tests to ensure safety and reduce exposure to product liability claims. At the same time, “green” companies promote their unwillingness to use the Draize test.

Experts were not aware of a reliable estimate of the number of rabbits currently used in the United States for the tests. Animal protection groups often refer to “hundreds of thousands,” and an industry-sponsored survey of toxicology labs published in 1987 put the number at 120,000. But Goldberg, of Johns Hopkins, said that figure has probably dropped significantly since then.

The cornea is the focus of toxicology tests because the thin, clear dome is the eye’s most vulnerable tissue.

Eye doctors also welcomed the invention as a harbinger of a possible new source of transplantable material, though there is not a crisis in the U.S. supply of transplantable corneas from cadavers.

“This is a very exciting possibility . . . this group has made a step in developing a bioengineered cornea that could ultimately be used for cornea transplants,” said Dr. Ronald Smith, chairman of ophthalmology at the USC School of Medicine and head of the Doheny Eye Institute. “They’ve made a good start,” he said of the researchers, but he cautioned that the strength, clarity, durability and transplantability of the tissue have not been tested.

In broad terms, the research, led by cell biologist May Griffith of the Ottawa Eye Institute in Ontario, represents progress in medicine’s venerable dream of repairing diseased organs and damaged body parts with complex tissues generated in labs.

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Experts described the engineering feat as remarkable, largely because the laboratory corneas--about half an inch across and resting in a chemical bath--so resemble the real thing. A cornea is deceptively complex, consisting of three layers of living cells supported by a matrix of collagen, the whole tissue being fed by tears and other fluids without benefit of blood vessels.

Previously, researchers managed to get cells from each of the three layers to grow in dishes, but no one had been able to assemble them into a functioning whole.

Griffith and her colleagues used three separate cell lines--each derived from discarded cadaver corneas not fit for transplanting--then supported them on a vanishingly thin matrix of collagen and another component of cartilage.

Electrophysiology tests showed that the cultured cornea conducted impulses like intact tissue, showed irritation when exposed to detergent, and, most important, was clear.

Griffith said the “cornea equivalent,” as they call it, was not strong enough to be transplanted and would require much additional work for that application. But, she said, “it’s a good break for people looking for alternatives to animal testing.”

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Seeing Is Believing

The eye’s most vulnerable part, the cornea, is a thin, transparent dome covering the pupil. It consists of collagen tissue and three layers of living cells. Scientists based in Canada have grown human corneal tissue in lab dishes.

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Source: Ottowa Hospital

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