Developments in Bioartificial Liver Research (July 2000)

“Developments in Bioartificial Liver Research” is a review article from 2000 that discusses the progress made in artificial liver technology up to that date. Its focus is on Bioartificial Livers (BALs), and their potential for helping individuals waiting for liver transplants. According to the paper, there are three requirements for a successful BAL: “(1) a viable and highly functional hepatocyte cell line, (2) a suitable bioreactor environment and peripheral control system, and (3) an effective extracorporeal circulatory system to incorporate an artificial liver system.” The article also discusses some of the issues that need to be dealt with to have a successful and lasting BAL. Many of the issues mentioned in 2000 are still relevant today when trying to develop a functional bioartificial liver. One of the major problems is trying to find hepatocytes suitable for BAL systems. These hepatocytes can be derived from animal cell lines or human cell lines. As learned in class, xenogenic transplantations, whether in the form of cells or whole organs, present numerous complications. Porcine hepatic cells are often used, but issues such as hetoroimmunity and infection often arise. Ideally, human hepatic cells would be used, but this is more complicated due to legal restrictions and a lack of sources. In 2000, a promising endeavor was implanting human hepatic genes into animal cells. This would take care of the proliferation issue, as well as some heteroimmunity problems. As seen today, this method has provided many benefits and is more commonly used than in the year 2000. With regard to these cell lines, the most important factor is that these cells should be able to proliferate for a prolonged period of time, minimize immune response, and produce the necessary proteins and chemicals that normal hepatocytes would. The article then discusses the three dimensional bioreactor consisting of the liver cells and a hollow fiber system through which the blood plasma is delivered. The bioreactor functions to eliminate toxins and deliver liver specific proteins into the blood stream. At the time of this article, the three dimensional bioreactor was in its earliest production and trial stages. Now, it is the accepted type of bioreactor that is most effective in performing liver functions compared to the 2D bioreactor system. In addition to the bioreactor component that this article focuses on, other aspects of the liver assist device are equally as important such as the anticoagulant, the plasma separator, and the oxygenator, among other parts. As mentioned before, the expanded use of such bioartificial liver systems would have a direct impact on healthcare costs. It is also interesting to think about whether such temporary treatment should be provided to all those suffering liver failure via Medicaid, similar to end stage renal disease and kidney dialysis. This article indicates that the year 2000 marks a significant progression in bioartificial liver technology. It is around this time that biotechnologists prioritized the efficacy and success of the production of liver cell related proteins in addition to detoxification of the blood.

-Mark

Seishi Nagamori, Journal of Gastroenterology, 7/07/00

http://www.springerlink.com/content/5edyeq1qb4f46cj9/