Stem Cell's at the Heart of Bioartificial Liver

Genetic Engineering and Biotechnology News, September 26, 2007

The successful removal of ammonia, a highly toxic by-product which causes brain damage, coma, and even death, and the production of urea was announced today by HepaLife Technologies, Inc. They developed a first-of-its-kind artificial liver device where the company's patented PICM-19 liver stem cells were placed inside its proprietary artificial liver device to produce the positive results.

"Today's results demonstrate that, while inside our bioartificial liver device, HepaLife's PICM-19 cells are able to produce substantial amounts of urea and remove toxic ammonia, while remaining healthy, and replicating important liver-like functions," stated Mr. Frank Menzler, President and CEO of HepaLife. "This is a significant achievement that marks a major milestone in the development of our artificial liver device."

"These new results have certainly exceeded our early performance expectations of the HepaLife bioartificial liver design. Our goal is to now further evaluate the HepaLife bioartificial liver system in-vitro and in-vivo, and continue to move closer to an application with the Food and Drug Administration for our cell-based device."

Similar to the functions mimicked by HepaLife's PICM-19 cells in today's research outcomes, the biological cells inside the device which are responsible for truly replicating and performing the functions of the human liver are the most vital component of the artificial liver device, not the actual mechanical hardware say researchers.

Over the entire duration of the study, the system successfully produced significant amounts urea and liver-specific protein such as albumin while removing toxic ammonia confirmed research data from experiments with the PICM-19 cells inside HepaLife's artificial liver device. Reaching peak levels at termination of the study after two weeks, the production of urea and albumin increased over time, marking the most important outcome of the study.

Since cells which are not contact-inhibited tend to become cancerous, an important indicator if normal cell growth was that the PICM-19 liver cells remained contact-inhibited. This confirmed earlier findings in observations of cell replication and growth. The HepaLife's PICM-19 cells inside its liver device system remained non-tumorigenic.

An indication of the cells' physical form and structure was observed in the same test. Normal morphology was displayed as the HepaLife's PICM-19 liver stem cells successfully differentiated into hepatocytes (liver cells).

Researchers analyzed levels of lactate and glucose -- indicators of metabolic function -- alongside oxygen and carbon dioxide, respectively, when evaluating the chemical function and overall health of the PICM-19 liver cells inside HepaLife's bioartificial liver system. Throughout the duration of the studies, these monitored levels remained favorably within targeted parameters in all cases.

"These results suggest that HepaLife's bioartificial liver system is an artificially created, 'living biosystem' -- our goal from the early beginning -- with cells that behave as we have long desired for our artificial liver device," concluded Mr. Menzler.

Intended for the treatment of liver failure, the HepaLife(TM) Bioartificial Liver device consists of three basic components: (1), the HepaDrive(TM), a perfusion system for pumping the patient's plasma through the bioreactor while controlling gas supply and temperature for best possible performance of the cells; (2)the bioreactor, a unit filled with PICM-19 cells which biologically mimic the liver's function; and (3) a plasma filter, separating the patient's blood into blood plasma and blood cells.

HepaLife is developing the first-of-its-kind bioartificial liver while incorporating the PICM-19 cell line. Designed to operate outside the patient's body HepaLife's bioartificial liver is currently under development. The bioartificial liver processes the patient's blood-plasma by removing toxins, enhancing metabolic function, and ultimately, imitates the liver's natural function.

The bioartificial liver is envisioned to mimic important functions of the human liver by circulating the patient's blood inside the device, where it is exposed to HepaLife's patented PICM-19 liver stem cells.