The first bioartificial liver device was developed in 1993 by Dr. Achilles A. Demetriou at Cedars-Sinai Medical Center. The bioartificial liver helped an 18-year-old southern California woman survive without her own liver for 14 hours until she received a human liver using a 20-inch-long, 4-inch-wide plastic cylinder filled with cellulose fibers and pig liver cells. Blood was routed outside the patient's body and through the artificial liver before being returned to the body. Dr Kenneth Matsumara's work on the BAL led it to be named an invention of the year by Time magazine in 2001. Liver cells obtained from an animal were used instead of developing a piece of equipment for each function of the liver. The structure and function of the first device also resembles that of today's BALs. Animal liver cells are suspended in a solution and a patient's blood is processed by a semipermeable membrane that allow toxins and blood proteins to pass but restricts an immunological response.
Development
Advancements in bioengineering techniques in the decade after Matsumara's work have led to improved membranes and hepatocyte attachment systems. As time has progressed the sources of hepatocytes have increased. Cell sources now include primary porcine hepatocytes, primary human hepatocytes, human hepatoblastoma, immortalized human cell lines and stem cells.
Use
The purpose of BAL-type devices, currently, is not to permanently replace liver functions, but to serve as a supportive device, either allowing the liver to regenerate properly upon acute liver failure, or to bridge the individual's liver functions until a transplant is possible.
Function
BALs are essentially bioreactors, with embedded hepatocytes that perform the functions of a normal . They process oxygenated blood plasma, which is separated from the other blood constituents. Several types of BALs are being developed, including hollow fiber systems and flat membrane sheet systems.
Hollow fiber system
One type of BAL is similar to kidney dialysis systems that employ a hollow fiber cartridge. Hepatocytes are suspended in a gel solution, such as collagen, which is injected into a series of hollow fibers. In the case of collagen, the suspension is then gelled within the fibers, usually by a temperature change. The hepatocytes then contract the gel by their attachment to the collagen matrix, reducing the volume of the suspension and creating a flow space within the fibers. Nutrient media is circulated through the fibers to sustain the cells. During use, plasma is removed from the patients blood. The patient's plasma is fed into the space surrounding the fibers. The fibers, which are composed of a semi-permeable membrane, facilitate transfer of toxins, nutrients and other chemicals between the blood and the suspended cells. The membrane also keeps immune bodies, such as immunoglobulins, from passing to the cells to prevent an immune system rejection.
The advantages of using a BAL, over other dialysis-type devices, is that metabolic functions, in addition to detoxification, can be replicated without the use of multiple devices. There are currently several BAL devices in clinical trials. A series of studies in 2004 showed that a BAL device reduced mortality by about half in acute liver failure cases. The studies, which covered 171 patients in the U.S. and Europe, compared standard supportive care to the use of a bioreactor device using pig liver cells.
