High hopes for lab-grown organs despite setbacks

SAN JOSE -- By manipulating cells in a laboratory, Stanford University researchers have created livers that closely resemble those of rats and pigs.

Executives at Cerco Medical of San Francisco have fabricated human islet cells into a patch the size of a business card that they believe one day could be attached to a diabetic's pancreas to make insulin.

And a Wake Forest University School of Medicine researcher has grown human bladders.

Yet after more than two decades of effort by biotechnology firms and nonprofit institutions, the dream of replacing people's defective organs and other body parts with lab-grown versions has largely remained unfulfilled.

Although investors have pumped more than $4.5 billion into so-called tissue engineering companies since 1990, according to federal estimates, only a smattering of lab-made skin and cartilage products have been approved for sale.

Moreover, while the number of such companies has steadily grown, many tissue engineering entrepreneurs have struggled to make a profit and some say it's gotten harder to attract private money for their businesses.

"I can't get the venture capitalists I've worked with for years to return calls," said Scott King, chief executive at Cerco Medical, one of the few companies in the Bay Area to dabble in the field. "There is just no interest," he added, noting that the lack of financing has forced him to temporarily halt studies of his insulin-producing patch.

Meanwhile, companies such as Cerco are facing increasing competition from foreign tissue engineering businesses, which tend to get a greater share of their money from government sources. As a result, "other countries may increasingly challenge U.S. leadership in this field," warned a report issued in June by several U.S. agencies.

About 20 years ago, when tissue engineering first took off in this country, the interest was primarily fueled by the dearth of hearts, kidneys, lungs, livers and other donor organs for transplants. That shortage has not eased.

Although nearly 30,000 people in the United States received such transplants last year, the waiting list for organs tops 100,000, according to the Organ Procurement and Transplantation Network, which Congress created in 1984.

Mechanical organs, metal hip joints and other synthetic body parts have helped fill the need. But such devices sometimes don't last as long as living tissue, and can cause blood clots and infection. So if firms could bioengineer replacements, many experts say, the potential profits could be huge.

A federal study three years ago estimated that the global market for bioengineered tissues and other so-called regenerative-medicine products could exceed $500 billion within two decades. Yet current annual sales of such products total only about $1.5 billion, according to Michael Lysaght, who tracks that data as Director of the Center for Biomedical Engineering at Brown University in Rhode Island.

That hasn't deterred a growing number of entrepreneurs from entering the field. Since 2000, the industry worldwide has grown from 70 companies with 3,100 full-time employees to about 160 firms with 6,100 employees today, Lysaght said. The annual investments by public and private sources also has risen over that same period, from about $610 million to $900 million.

Still, experts say profits have remained elusive for most tissue-engineering companies in this country, including Advanced Tissue Sciences of La Jolla. It managed to get a product for treating burns approved for sale by the U.S. Food and Drug Administration in 1997 and another approved in 2001 for treating ulcers and other wounds. Yet the products generated little revenue and the company filed for bankruptcy in October 2001.

"What's happened has been terrible," said Gail Naughton, who co-founded the company in 1987 and now is dean of San Diego State University's College of Business Administration.

She attributes Advanced Tissue Sciences' failure to a variety of factors, but said it partly reflected a tendency many early tissue-engineering businesses had of overestimating how much hospitals and insurers would pay for their products.

"We were all making it up as we went along," she said. "Anytime you are the first ever, there are going to be challenges."

Nonetheless, many companies and research institutions are still pursuing the hope that organs and other body parts one day can be grown like so much farm produce to rejuvenate patients suffering from a wide range of ailments.

"The science is advancing," said William Wagner of the McGowan Institute for Regenerative Medicine in Pennsylvania. "The level of sophistication you see in the scientific literature has markedly increased in the last five years."

The variety of potential applications for lab-grown tissues is seemingly limitless.

Some Japanese researchers reported in March that they have developed a promising technique for growing whole teeth.

The military is studying ways to grow tissue to replace burned skin, repair damaged limbs and even detect biological or chemical warfare agents.

Still other efforts are under way to develop bioengineering heart valves, breasts, vaginae, nerves, blood vessels and bone.

But the greatest goal remains to make whole replacement organs for people, said Dr. Geoffrey Gurtner, the Stanford researcher who has grown the rat and pig livers.

"That is in the long term, where tissue engineering will really be important," he said. "It will be a game-changing paradigm in medicine."