Liver support system

Although certain simple functions of the liver, such as the removal of some toxins, can be performed by using dialysis and adsorption with activated charcoal, it is clear that such a simple artificial approach cannot perform the complex functions of the liver, and that any practical liver support system must use living hepatocytes. It should be mentioned at this point that hepatocytes have an anchorage-dependent nature that is, they require a form of anchor (i.e., a solid surface or scaffold) on which to grow. Thus, the use of single-cell suspensions is not appropriate for liver cell culture, and fiver cells attached to solid surfaces are normally used. Encapsulated fiver cells and spheroids (i.e., spherical aggregates of fiver cells) may also be used for this purpose. 

Mazariegos, G.. Kramer, D.. Lopez, R., Shjakil, A., Rosenbloom, A., DeVera, M., Giraldo, M., Grogan, T, Zhu. Y. Fulmer, M., Amiot, B., Patzer, J. Safety observations in phase I clini cal evaluation of Excorp medical bioartificial liver support system after the first four patients. ASAIO J. 47, 471, 2001. 

The Vitagen project using immortalized hepatic cells in a hollow fiber capsule in combination with a carbon-based toxin removal system is worthy of special note. The ELADTM bioartiflcial liver support system is designed to combine the unique... 

Artificial liver support systems aim at the extracorporeal removal of water soluble and protein-bound toxins (albumin being the preferential binding protein) associated with hepatic failure. Albumin contains reversible binding sites for substances such as fatty acids, hormones, enzymes, dyes, trace metals and drugs [26] and therefore helps elimination by kidneys of substances that are toxic in the unbound state. It should be noticed that the range of substances to be removed is broad and not completely identified. Clinical studies showed that the critical issue of the clinical syndrome in liver failure is the accumulation of toxins not cleared by the failing liver. Based on this hypothesis, the removal of lipophilic, albumin-bound substances, such as bilirubin, bile adds, metabolites of aromatic amino acids, medium-chain fatty acids, and cytokines, should be benefidal to the dinical course of a patient in liver failure. 

Support systems Artificial renal and liver support systems may also be considered in order to bridge the period of time until liver transplantation is performed, (l)... 

First clinical use of a novel bioartificial liver support system (BLSS). Amer. X Transplant. 2002 2 260—266... 

Rahman, T.M., Hodgson, H.J.F. Review article liver support systems in acute hepatic failure. Aliment. Pharm. Then 1999 13 1255-1272... 

Tsiaonssis, X, Newsome, P.N., Nelson, L.X, Hayes, P.C., Plevis, XN. Which hepatocyte will it be Hepatocyte choice for bioartificial liver support systems. Liver Transplant. 2001 7 2-10... 

The mortality rate depends on the cause of disease, the patient s age as well as the intensity and duration of encephalopathy. Since the introduction of liver transplantation and temporary liver-supporting systems, the mortality rate in acute liver failure has been reduced markedly. (48)... 

Yanagi, K. Ookawa, K. Mizuno, S. Ohshima, N. Performance of a new hybrid artificial liver support system using hepatocytes entrapped within a hydrogel. ASAIO Trans. 1989, 35 (3), 570-572. 

Mullon, C. Soloman, B.A. HepatAssist liver support system. In Principles of Tissue Engineering, 2nd Ed. Lanza, R.P., Langer, R., Vacanti, J., Eds. Academic Press New York, 2000 553-558. 

Stange J, Hassanein TI, Mehta R, et al. The molecular adsorbents recycling system as a liver support system based on albumin dialysis a summary of preclinical investigations, prospective, randomized,... 

In recent years, many investigations have been conducted, including clinical trials, with bioartificial liver devices using either animal or human liver cells. Likewise, many reports have been made with various designs of bioartificial liver device [19]. However, there are no established liver support systems that can be used routinely in the same way as hemodialyzers or blood oxygenators. Today, bioartificial liver devices can be used to assist the liver functions of patients with liver failure on only a partially and/or temporary basis. Moreover, none of these devices can excrete bile, as does the human liver. 

Galletti, P. M. and H. O. Jauregui, 1995, Liver support systems, in The Biomedical Engineering Handbook, J. Bronzino, ed., CRC Press, Boca Raton, FL, pp. 1952-1966. 

Moolman F. Mass transfer considerations, in oxygen carriers for a novel bio-artificial liver support system, Moolman F, editor. Germany Verlag Dr. Muller 2003, p. 130. 

University of Berlin Hybrid Organ GmbH, Berlin, Germany Modular Extracorporeal Liver Support System (MELS) Extracorporeal liver-failure treatment Hepatocyte bioreactors... 

A hybrid artificial liver support system was developed using hepatocytes entrapped within a calcium alginate hydrogel (137). The module was designed in imitation of the gas-liquid contactor that uses the same principle. Forty disks with film-shaped hydrogel were mounted to a horizontal rotating axis and were kept in contact with blood. The concentration of hepatocytes in the gel varied from 1.9 X 10 to 1.7 X 10 cells/L of gel. The results of ex vivo perfusion experiments using cats with acute hepatic insufficiency indicated that this module has the ability to replace liver function. 

Krasteva, N., Harms, U., Albrecht, W., Seifert, B., Hopp, M., Altankov, G., and Groth, T. (2002). Membranes for biohybrid liver support systems—Investigations on hepatocyte attachment, morphology and growth. Biomaterials 23(12), 2467-2478. 

Liver Support Systems Matthew S. Chang and Robert S. Brown, Jr. 

The bioartificial liver support devices that are under investigation include the extracorporeal liver assist device (ELAD, Vital Therapies, San Diego, Cahfornia, USA) and the HepatAssist Liver Support System (HepaLife Technologies, Boston, Massachusetts, USA). 

Pless G. Bioartificial liver support systems. Methods Mol Biol 2010 640 511-23. 

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