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In-Vitro Toxicology Testing
Drug Induced Liver Disease In-Vitro Toxicology Testing PICM-19 Cell Line Publications
Prescription drug side effects account for 200,000 deaths each year, and drug toxicity is the single most common reason for the FDA to deny approval or withdraw a drug from market. The PICM-19 cell line is the basis for a much-needed improved pre-clinical drug toxicity test.
Drug Induced Liver Disease - Improved testing tools needed
More than 6,000 Americans suffer drug toxicity each day in hospitals. Sadly, nearly 80,000 children are admitted to hospitals as a consequence of adverse drug reactions, with almost 40% of such cases classified as 'life-threatening'.
Acetaminophen, the active ingredient in Tylenol®, is one of the main culprits. In 2004 and 2005 alone, acetaminophen has caused 51% of all acute liver failure. It is the most commonly used pharmaceutical analgesic and antipyretic agent in the world.
What's more, the inability to accurately predict toxicity early in drug development cost the pharmaceutical industry a record $8 billion in just one year, 2003. In particular, hepatotoxicity, or liver damage caused by medications and other chemical compounds, is the single most common reason leading to drug withdrawal or refusal of drug approval by the FDA. In fact, about one third of all potential drugs fail pre-clinical or clinical trials due to the toxic nature of the compounds being tested, accounting for an estimated $70 million (20%) of total research and development costs per drug.
Despite efforts to develop better methods, most of the tools used for toxicology are decades old and there is still no effective way to test a compound's safety on human livers.
HepaLife's In-Vitro Toxicology Testing
 PICM-19 in-vitro toxicity assays are adapted for use in high throughput screening. |
HepaLife is developing in-vitro toxicology testing platforms to determine the potential liver toxicity and metabolism of new pharmacological compounds and drugs.
Drug metabolism is the chemical alteration of a drug by the body as it is processed by various organs. The liver is the principal site with essential enzymes for this metabolic action. After entering the body, a drug is eliminated either by excretion or by metabolism to one or more active or inactive metabolites. So called cytochrome P-450 enzymes metabolize the drugs through oxidation.
Hepalife's PICM-19 cell mimic important functions of the human liver and of its enzymes. The PICM-19 cells grown in vitro synthesize liver specific proteins such as albumin and transferrin, and display enhanced liver-specific functions such as ureagenesis. Cytochrome P450 activity.
HepaLife, using its patented PICM-19 cell line, targets to more accurately determine the potential toxicity and metabolism of new pharmacological compounds in the liver.
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HepaLife's PICM-19 embryonic liver stem cell line derived from the pig epiblast is the only cell line of its kind with full expansion and growth capacity, maintaining its hepatic function in repeated passage.
Importantly, these cells have the ability to uniquely differentiate into hepatocytes (liver cells) and/or bile duct epithelium.
Unlike other cell lines, HepaLife's PICM-19 remain fully functional and do not become tumorigenic or cancerous, despite years in continuous culture. PICM-19 cells synthesize high amounts of ammonia and produce substantial amounts of urea in an in-vitro system. They exhibit enhanced liver-specific functions for proprietary pre-clinical drug testing platforms, developed for improved accuracy in determining the potential liver toxicity and metabolism of new pharmacological compounds. Additional features of the PICM-19 cells line include:
- Express high levels of inducible P450 and GGT; important indicators of hepatocyte and bile duct functions, respectively
- Express proteins and mRNA that are unique to the liver
- Exhibit in-vivo-like response of in-vitro produced ductules to secretin and cAMP inducers
- Detoxify high amounts of ammonia and synthesize urea and/or glutamine, vital functions of the human liver
- Exhibit in vivo-like responses to common drugs and toxins (e.g., acetaminophen, rifampicin, etc.)
- Tolerate room temperature for prolonged periods of time while retaining hepatic function which enables convenient handling and shipping
- Willard RR, Meekin, Talbot NC, Caperna TJ: Characterization of PICM-19H Porcine Liver Stem Cell Line for Potential Use in a Bioartificial Liver, 54th ASAIO Annual Conference, San Francisco CA, June 19-21, 2008
- Willard RR, Meekin JH, Peters GW, Baun MJ, Gerlach JC, Talbot NC, Caperna TJ: Maintenance of Hepatic Cell Function by the PICM-19H Porcine Liver Stem Cell Line Cultured in a Bioartificial Liver, 6th ISSCR Annual Meeting, Philadelphia PA, June 11-14, 2008
- Talbot NC, Blomberg le A, Mahmood A, Caperna TJ, Garrett WM: Isolation and characterization of porcine visceral endoderm cell lines derived from in vivo 11-day blastocysts, In Vitro Cell Dev Biol Anim. 2007 Feb;43(2):72-86
- Talbot NC, Caperna TJ, Wells KD.: The PICM-19 cell line as an in vitro model of liver bile ductules: effects of cAMP inducers, biopeptides and pH, Cells Tissues Organs. 2002;171(2-3):99-116
- Talbot NC, Caperna TJ, Lebow LT, Moscioni D, Pursel VG, Rexroad CE Jr.: Ultrastructure, enzymatic, and transport properties of the PICM-19 bipotent liver cell line, Exp Cell Res. 1996 May 25;225(1):22-34
