Artificial liver an alternative to toxicity testing

Related tags Liver

Bioengineers at the University of Oxford have developed a solution
to the problem of toxicity testing for new drugs, which can prove
to be ineffective or at worst dangerous to humans.

The Tissueflex is a combination of a 3D bioreactor system and silicone multiwell technology. The bioreactor can be adapted to produce a number of different types of body tissue but it is the culture of artificial liver cells, primarily for use in toxicity testing that is an important aspect.

The drug development process from the discovery of an optimised lead then on to market is typically a seven to ten year process with costs exceeding $800 million (€625 million). It is well known to be an expensive process with a high risk of failure as recent high profile cases have shown.

Merck's drug Vioxx, used to treat arthritis, was withdrawn from the market in October after comprehensive clinical data confirmed long-established concerns that the treatment could increase the risk of heart attacks and strokes.

The Tissueflex system is able to facilitate growth of in-vitro tissue in 3D. 2D cell culture has been the preferred method of cell culture for biologists because it is easier to grow with existing equipment than 3D. However, cells behave differently in 2D and 3D structures and 2D cultures do not always give accurate results.

Sourcing of human hepatocytes for in vitro assays has long been a problem in pharmaceutical drug development. They have traditionally been sourced from cadavers or cancer resections, but supply of these cells is limited and their characteristics vary widely among the sourced donors.

Additionally, hepatocytes cannot be sustained in culture without losing function, so they must be continually sourced. Hence, pharmaceutical companies have had to rely heavily on animal models for preclinical metabolism and toxicity testing, but even these are often not predictive for man.

By using Tissueflex and its hollow fibre membrane bioreactors the problem of adequate oxygenation and appropriate transport of nutrients to, and waste products from the tissue, overcomes the limitations of diffusive transport to grow the three-dimensional tissue structures required.

Tissueflex incorporates a hollow microfibre perfused design maintaining control over levels of all key parameters. This is crucial as variability in flow rate, nutrient concentration, growth factor concentration and scaffold material selection. Once the biological design has been set the Tissueflex can be adapted for integration in automated analysis systems.

A feature of the Tissueflex allows monitoring of conditions ensuring enhanced data and accelerated development. The gas permeable nature and physical properties of the materials used ensure that access to the sample can be obtained for testing, while preserving sterility and maintaining effective gas exchange.

Tissueflex's system has been developed to be both transparent and tough. Its bioreactors can also be autoclaved. The design can be customised to allow optimisation of cell size, geometry, hollow fibre membrane type and spacing to be made. Many cells can be provided in parallel for more efficient testing.

The concept of using an artificial liver, particularly in the pharmaceutical testing and development of compounds into bona-fide drug treatments is not a new one. With the demand for a better system to screen compounds in simulated environments, companies, which can develop an artificial organ that can recreate the effects of a drug, are likely to do very well financially.

MultiCell Technologies,​(formerly Exten Industries) is a medical products company that focuses on the production and application of immortalised human liver cells in the treatment of liver disease and production of cell lines for testing new pharmaceutical products in development.

Likewise, HepaLife Technologies​ is an early stage biotechnology company focusing on developing the first of its kind artificial liver device and proprietary in vitro toxicology and preclinical drug testing platforms.

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