Initial experience with the modified extracorporeal liver-assist device for patients with fulminant hepatic failure: system modifications and clinical impact

Abstract

The patients tolerated treatment with the ELAD well. There were no unanticipated safety issues. The cells in the cartridges were metabolically active. All patients successfully underwent transplantation. The results from this single-institution experience indicates that larger randomized multicenter trials should proceed.

Current development of bioreactors for extracorporeal bioartificial liver (Review)

“…148 ͑2͒ To simulate the in vivo microenvironment of liver tissue and provide consistent and sufficient support for long-term maintenance of liver cell function and viability, by ͑a͒ the improvement of the oxygen supply by independent channels for oxygen supply, amendment of extra oxygenators to the system; 148 or expansion the distribution of oxygen;…”

“…152 the addition of the oxygen carriers such as calf red blood cells, 165 perfluorocarbons; 166,167 ͑b͒ Optimization of the bioreactor microenvironment, by mimicking the oxygen and nutrient concentration gradient of liver tissue in vivo, which may be helpful for the liver cells to re-establish their performance before isolation; 168 ͑c͒ improvement of the technology of hepatocyte isolation and cultivation, such as coculture with nonparachymal cells to enhance hepatocyte function; investigation of the advanced material and construct of the supportive scaffold; ͑3͒ to facilitate dynamic monitoring the changes of function and biochemical parameters within the bioreactor; 148 and ͑4͒ to be easy for cryopreservation, transport, and assembly to fully suit the clinical practice. 1 52 T. Hoshiba, H. Nagahara, C. S. Cho, Y. Tagawa, and T. Akaike, Biomaterials 28, 1093 ͑2007͒.…”

“…To further enhance the safety and efficacy of ELAD, Millis et al 148 modified its bioreactor in the following aspects: ͑1͒ to promote the mass exchange between the plasma and the cells, the semipermeable membrane pore size was increased from 70KD to 120KD, and the perfusion rate of 150-200 ml/min was changed into 500 ml/min; ͑2͒ to increase the cell mass from 200 to 400 g; ͑3͒ to set the online dynamic monitoring of oxygen and glucose consumption in the bioreactor in order to understand the metabolic activity of the liver cells; ͑4͒ to add an extra filter in the circulatory system to prevent the cell leakage into patient; and ͑5͒ to amend the oxygenation device in the system for further improvement of the oxygen level in the bioreactor. With these improvements, C3A cells in the ELAD system can maintain effective metabolic activity even after 12-107 h of treatment.…”

Interaction between hepatocytes and collagen gel in hollow fibers

“…The providing of nutritions was largely determined by diffusion across the 3D gel-cell matrix (Millis et al 2002;Legallais et al 2001). Thus, the diffusion coefficient across gel-cell matrix has been extensively explored and we summarized these results in Table 2.…”

Scientific and industrial status of tissue engineering

“…All these products are in the clinical trial stage including Extracorporeal Liver Assist Device (ELAD): the study on this product started by Vitagen company (USA) (formerly called Hepatix) and is continued by Vital Therapies (USA) (Millis et al, 2002;Millis et al, 1999;Ellis et al, 1996;Sussman et al, 1994); HepatAssist: this product was initially developed by Circe Biomedical (USA) but has been handed over to Arbios Systems (USA) (Demetriou et al, 2004;Watanabe et al, 1997;Demetriou et al, 1995); Bioartificial Liver Support System (BLSS) by Excorp Medical (USA) Mazariegos et al, 2001;Kuddus et al, 2002); and Modular Extracorporeal Liver System (MELS) by Hybrid Organ (USA) (Sauer et al, 2003b;Sauer et al, 2003a). (Grosset and Grosset, 2005;Bakay et al, 2004).…”