History of ACTIVTox
Development of the ACTIVTox platform
ACTIVTox, our in vitro, C3A–based cell system was created to address the difficulty of obtaining primary human hepatocytes combined with the problems of HepG2 reliability and reproducibility. ACTIVTox meets the needs of emerging high throughput drug screening and environmental toxicity testing.
Superiority of C3A Hepatocytes
The C3A line was chosen because it has the essential structural, biochemical, and growth features of normal human liver cells. The C3A hepatocyte cell line is a patented, highly selected subclone of Hep G2 that retains many of the properties of the normal human hepatocyte (1). C3A hepatocytes exhibit strong contact inhibition at confluency, high expression of albumin (generally 25µg/mg total cell protein/24 hrs) and high albumin/alpha-fetoprotein at confluency (usually 25µg/mg total cell protein/24 hrs).
Phase contrast of C3A cells.
The C3A cells are handled using established cell banking techniques and rigorous quality control that provides a continuously renewable source of standardized material. The advantages of using the C3a cell line have been documented and summarized (2):
- C3A hepatocytes are a homogenous population; HepG2 cells are not.
- C3A hepatocytes have propagated and proliferated under rigourously controlled conditions; HepG2 cells have grown uncontrollably for 30 years.
- C3A hepatocytes have a phenotype that can be maintained indefinitely; HepG2 cells do not.
ExtraCorporeal Liver Assist Device (ELAD)
In the early 1990's, the C3A cells were placed in a kidney dialysis cartridge to form an extracorporeal liver assist device (ELAD®) that was connected to human patients with various types of end-stage liver disease (3).
Reference
- Kelly, J.H. (1994) Permanent human hepatocyte cell line and its use in a liver assist device (LAD), US Patent No.5,290,684.
- Kelly, J.H., and Sussman, N.L. (2000) A fluorescent cell-based assay for cytochrome P–450 isozyme 1A2 induction and inhibition. J. Biomol. Screen 5(4): 249–254.
- Sussman, N.L., Gialason, G.T., Conlin, C.A., and Kelly, J.H. (1994) The Hepatix extracorporeal liver assist device: initial clinical experience. Artificial Organs 18: 390–396.
