A new bioartificial liver designed by HepaLife Technologies, integrated with pig-epiblast derived PICM-19 liver stem cells, showed positive outcomes for quick elimination of toxic levels of ammonia in vitro, according to a company press release.
The essential elements of HepaLife™ Bioartificial Liver Device, developed for the treatment of acute liver failure, includes a plasma filter for segregation of patients’ plasma from blood cells, a bioreactor for producing urea whilst retaining hepatic functions using PICM-19 liver stem cell lines, and a perfusion system called the HepaDrive™ for pumping the plasma through the bioreactor and maintaining the optimum conditions of gas supply and temperature, essential for achieving best results from hepatic cells.
Recent studies conducted on this bioartificial liver has shown that apart from detoxification of ammonia by 75% in less than 24 hours, the company’s patented liver stem cell lines facilitated the conversion of almost 80% of ammonia into urea through the natural urea cycle. The PICM-19 stem cells also demonstrated the ability to perform differentiated hepatic functions, with characteristic human hepatocyte morphology, such as endoplasmic reticulum, Golgi apparatus, intercellular canaliculi, mitochondria, and peroxisomes.
PICM-19 porcine embryonic liver stem cells simulate in vivo liver regeneration by differentiating into mono-layers of fetal hepatocytes or bile ductules. The hepatic functions, similar to those in human liver, are retained for many years with continuous culturing. The major hepatic functions demonstrated by PICM-19 cells include:
The cells also maintained hepatic functions at room temperature for an extended time period for the convenience of handling and shipping.
Xu et al (Annals of Clinical and Laboratory Sciences, 2003) conducted an in vitro study to determine the efficacy of an internal bioartificial liver, consisting of pig-derived liver cells, for detoxification and performing other metabolic functions. Porcine hepatocytes were either attached to a microcarrier, or perfused into a polysulfon hollow fiber to create the artificial liver. The study was conducted in four cell culture groups, including a control group, a microcarrier group, a hollow fiber group, and an internal bioartificial liver group. Several parameters such as alanine aminotransferase (ALT) and lactate dehydrogenase (LD) activities in the medium, diazepam transformation, glucose-6-phosphatase activity of cells, hepatocyte viability, protein synthesis, and urea production were observed during the culture period of 7 days. The results of the study demonstrated that the internal bioartificial liver group maintained the hepatocyte viability for more than 80% during the culture period, with lower activities of ALT and LD, compared to the control or the microcarrier group. Functions such as protein synthesis and detoxification were also observed in the internal bioartificial liver group.
Various types of bioartificial livers, such as hollow fiber systems and flat membrane sheet systems, are being designed for treating liver complications. The bioartificial liver appears to be superior to liver dialysis, especially since the process of metabolism and detoxification can be performed within a single device.
Drug overdoses, infection with hepatitis viruses, and toxicity or other conditions that influence the normal flow of blood in the liver are some of the common cause of acute liver failure. The newly designed bioartificial liver with PICM-19 liver stem cells could be used in liver failure patients to provide extracorporeal temporary support until the condition of the patient is stabilized or until a donor organ is available for transplantation.
About HepaLife Technologies – Massachusetts based biotechnology company, HepaLife Technologies Inc, has a portfolio that includes artificial liver devices, in vitro toxicology testing, and influenza vaccines. The company works ion programs with patented cell-based technologies in order to improve the quality of life of patients with hepatic disorders and also works on programs to combat the pandemic flu.
References
1. HepaLife’s Bioartificial Liver Dramatically Reduces Toxic Marker for Acute Liver Failure. Press Releases. HepaLife™. Last accessed on February 13, 2008.
2. Artificial Liver. Our Portfolio. HepaLifeâ„¢. Last accessed on February 13, 2008.
3. Xu Q, Yu D, Qiu Y, Zhang H, Ding Y. Function of a new internal bioartificial liver: an in vitro study. Annals of Clinical and Laboratory Sciences. 2003 Summer;33(3):306-12.
