Humes’s success is raising hope among corporate and academic researchers who are busy developing similar temporary-support devices for patients in acute liver failure, a rarer yet even more deadly condition. An acute case of hepatitis or a chemical assault (most commonly an overdose of the pain reliever acetaminophen) causes acute failure in about 2,000 people in the United States each year. Without transplants, nearly 80 percent will die, as ammonia and other toxins in the blood degrade the blood-brain barrier, causing the brain to swell out of control. Liver-assist devices analogous to Humes’s bioartificial kidney are already in advanced human tests, but despite years of development, definitive success has been elusive.
Bioartificial livers employ a cartridge full of liver cells to break down toxins in blood plasma fed into hollow plastic fibers. By taking over liver function, these devices could allow patients’ ailing organs to recover-or at least support them until transplant organs become available. George Mazariegos, a transplant surgeon at the University of Pittsburgh’s Thomas E. Starzl Transplantation Institute believes such devices might one day do more than carry patients through the most acute phase of liver failure; he hopes that by continuing to support patients for several weeks, bioartificial livers will enable an increasing number to recover the function of their own livers, avoiding the ordeal of transplantation and freeing up donor organs for those in greater need. “Cell-based therapies are going to be part of the mix, for sure,” he says.
Finding the right cells may be the key to success. The earliest bioartificial-liver devices used liver cells from pigs to detoxify blood, but concerns over the possible transfer of porcine viruses to humans-unlikely as many researchers considered it to be-frightened investors and dried up financing for these projects. In March, investors pulled the plug on yet another bioartificial-liver company. San Diego-based Vitagen was in advanced clinical trials with a device employing cells cultured from a human liver tumor. These cells had been “immortalized,” meaning they could be multiplied ad infinitum-so they were easy to come by. There are risks attached to using tumor-derived cells, however, and more significantly, the cells had less-than-normal liver function. Nonetheless, the technology was showing promise in trials, which were halted by the company’s demise.
Normal human liver cells clearly would be preferable. Immortalized liver cells retain a youthful capacity for growth because they are frozen in an early stage of development, but as a consequence they have not attained some of their most important detoxification tricks. “Immortalized cells are blocked in their ability to mature, so their ability to support patients is minimal,” says Lola Reid of the University of North Carolina at Chapel Hill. Reid says that what is needed are young yet normal human cells, akin to Humes’s immature kidney cells, that can grow and develop to populate a bioartificial device. To that end, she is developing cell-handling methods to isolate and amplify immature liver cells from donor organs.
Improvements in device design will help deliver more metabolic firepower as well. Jrg Gerlach, who recently moved to the University of Pittsburgh’s McGowan Institute for Regenerative Medicine from Berlin’s Charit Institute for Transplantation and Organ Regeneration, has developed a bioartificial liver that employs three types of hollow fibers woven through human liver cells harvested from transplant rejects. One set of fibers delivers oxygen to the living cells, keeping them in metabolic overdrive, while the other two pump plasma respectively to and from the cells, a setup that resembles the natural architecture of the liver. “Our cells spontaneously reassemble into tissue structures. Under these circumstances, the human cells survive for more than two months,” says Gerlach, who has already initiated human tests of the device in Germany. Larger trials in the United States could begin within a year.