A group of researchers from Massachusetts General Hospital (MGH) seem to have developed a novel method in order to culture liver cells for screening of drug toxicity. Researchers claimed that better and quicker ways to screen drugs for toxic side effects may be able to considerably decrease the cost and expense of bringing novel drugs in to the market.
In addition, it would reduce sudden unfavorable proceedings which seem to take place when new agents move from the clinical trial stage into broader use. According to them, liver cells which are grown in a high-oxygen surrounding and in a culture medium free of animal-derived serum could rapidly begin to function as they do inside the liver.
Since the liver is known to play an essential role in the metabolism and clearance of drugs, screening for liver toxicity is believed to be a crucial step in assuring the safety of novel agents. However, studies in animals appear to be only at times successful in predicting toxic liver effects. Also, freshly cultured liver cells may rapidly lose their metabolic competence under normal culture methods.
“Finding a better way to culture liver cells has been a major stumbling block in the development of predictive drug-discovery tools. We needed to develop an environment in which liver cells behave as they do in the body,” says senior investigator, Yaakov Nahmias, PhD, of the MGH Center for Engineering in Medicine (CEM).
Previous researches by the CEM team and others suggested that animal-derived serum could possibly obstruct the metabolism of cultured liver cells. Animal-derived serum appears to be commonly used in cell cultures.
Researchers speculated that a high-oxygen, serum-free culture environment apparently is the answer. In view of the fact that one of the key stresses involved in moving cells from an in vivo environment into culture seems to be a tenfold decrease in oxygen levels.
Their experiments initially confirmed that serum seems to interfere with the metabolism of cultured rat and human liver cells. Furthermore, the findings revealed that liver cells grown with endothelial cells in a serum-free culture with approximately 95 percent oxygen appears to have quickly carried on normal metabolic activity. Supposedly, the normal metabolic activity includes gene expression and cell function.
These cultured cells were believed to have successfully predicted the clearance rates for rapid as well as slow acting drugs. Additionally, they were noted to have maintained a high level of metabolic activity for several weeks.
“This is a significant achievement. Oxygen had been thought to affect cell survival but not gene expression or the function of cultured liver cells. This all changed when we started looking at new formations of culture media,” says a co-instigator of the PNAS study, Martin Yarmush, MD, PhD, director of the MGH Center for Engineering in Medicine.
The novel culture system seems to have been licensed to HμREL Corporation of Beverly Hills, California, a company developing human-relevant models of drug metabolism. Researchers anticipate that potential work may perhaps investigate in extending these results to other cell systems and clinical applications, such as transplantation of liver cells.
The findings of the research have been published online in the Proceedings of the National Academy of Sciences.