May 10,2001 SAN DIEGO (AP) - Scientists have coaxed liver cells into thriving on a specially machined silicon chip, a melding of biology and technology that could lead to the creation of an artificial liver device that would eliminate the need for transplants.
The team at the University of California, San Diego, says it has succeeded in keeping rat liver cells alive and fully functional on the special chips for at least two weeks. In prototypical artificial liver devices now being clinically tested, liver cells - which can be notoriously finicky - often survive only hours or days.
For the experiment, the team used silicon wafers - the same blanks used to make computer chips - etched with tiny wells no wider than a human hair that snugly house the individual cells. The rest of the wafer is riddled with pores of various sizes that allow nutrients and chemicals to flow through the chip, but blocking the larger bacteria and viruses.
"This is a very fundamental kind of a project: What can we do to make cells happy and to keep them growing?" said Michael J. Sailor, a professor of chemistry and biochemistry at the university.
The team presented the chip at the recent annual meeting of the American Chemical Society in San Diego.
The team foresees a day when stacks of the chips, perhaps a square yard's worth, could be combined to form an artificial liver that would cleanse the body's blood of toxins. As many as 300,000 liver cells can live on a patch of the special chips just 0.16 square-inch (1-square-centimeter) in area. The chips have not yet been harnessed to substitute the blood-cleansing role of a real liver.
Dr. Achilles Demetriou, chairman of the department of surgery at Cedars-Sinai Medical Center in Los Angeles, said that environment will put the chips to the test.
"We can now with very cheap, low-tech systems, keep cells alive in culture for weeks. The issue with any new device is what happens when those cells are exposed to toxic plasma, which is similar to what you see in a patient with severe liver failure," said Demetriou, who helped developed an artificial liver that uses pig cells.
If such a stacked-chip system could be devised, it could keep alive patients suffering from liver failure while they await a transplanted organ - or longer to allow their livers to naturally regenerate.
"Clinically, we need at least a week to keep our patients alive until an organ is available, or ideally six weeks because your liver can regenerate, in which case actually you don't need a whole organ transplant," said team member Dr. Sangeeta N. Bhatia, who teaches medicine and bioengineering at the university.
Dr. Eli Friedman, editor of the journal of the American Society for Artificial Internal Organs, suggests remaining "sedated and subdued" about the prospect of artificial livers, a field he's followed for 40 years. At present, some half-dozen companies worldwide have artificial liver devices in clinical trials.
"The liver still remains a black box, because we haven't yet as nicely defined what the liver does as we have the kidney," Friedman said.
Doctors fear the estimated 4 million Americans who are infected with the hepatitis C virus - many unknowingly - will lead to a dramatic rise in the number of people requiring liver transplants in future decades. The virus can lie dormant in the body for up to 30 years before flaring up to cause cirrhosis, liver failure and liver cancer.
The chips could also be fitted with an array of tiny sensors that could cater to the cells' every whim, adjusting, say, temperature and nutrient levels automatically and signaling doctors when anything goes awry.
"We want to have some way the cells can report to us if they're happy or not," Sailor said.
Such an ability would ensure a near-term goal of the team, which is to press the chips into use as miniature laboratories for the testing of experimental therapeutic drugs. Rather than test on animal subjects, scientists could use so-called bioreactor chips to determine the toxicity of novel drugs and how the liver processes them.
Copyright 2001 The Associated Press. All rights reserved.