Challenges - Why is there no bioartificial liver yet?
Some may ask why bioartificial liver development has been slow. A 2001 article
suggests that progress has been slow due to the number of variables to choose
from in designing a bioartificial liver.
One reason for the limited progress in the assessment of artificial-liver systems is the plethora of options and variables to be tested, which include use of hepatocytes or not, choice of cell-source and cell-line, bioreactor design, incorporation of filtering and charcoal columns, and which patients to study and for how long. (Hayes et al. “What Progress with Artificial Livers?” The Lancet. Oct 2001. 358(9290): 1286-1287.)
Other issues include the use of non-human cells and the possible transmission of virus from animals to humans, and more fundamentally, the vast number of functions performed by the liver, some of which are yet to be completely understood.
Currently, human trials have been limited to extracorporeal devices that filter the blood much like hemodialysis machines. If this work progresses, we may see even more similarities between the treatment of live failure and kidney failure.
The future of bioartificial liver work may be seen in a French study by Vianney et al. that describes their experiments with an implantable bioartificial liver device. The device uses inbred, allogeneic rat hepatocytes as donor cells. The researchers created a hollow-fiber device with these cells that they implanted into the peritoneum of the rats to be studied. Liver failure was induced by removing 95% of the liver tissue in 300 g rats. Control rats with no implantation and empty device-implantation were used. The results were encouraging: the devices reduced the rate of death of liver-compromised rats. Anticoagulation was not required, and the rats were sustained long enough for their livers to grow back.
The problems with this approach include some mentioned by the researchers, and others that have been challenges for the bioartificial liver field in general. A previous study of this type found fibrosis development around the capsules. They also noted that proteins larger than the pore size of the device cannot be released by the hepatocytes, limiting the efficacy of the device.
One major hurdle to implementing this therapy in humans is the size requirements of the device. The device they created had hollow fibers with hepatocytes seeded at a density of 5 million per meter. This article stated that the human body can be sustained on about 50 billion hepatocytes. This would mean that a human device would have to contain thousands of meters of hollow fibers. This space is familiar to researchers in the field of the implantable artificial kidney, in which similar problems have impeded research. Since the liver receives approximately 25-30% of the body's cardiac output compared to the kidney (about 20%), an implanted device would have a formidable task to accomplish.
Vianney Roger et al., Annals of Surgery Volume 228, Number 1, July 1998
Sherwood, Lauralee. Human Physiology: From Cells to Systems. 3rd ed.
Boston: Wadsworth, 1997
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