More effective treatments for liver disease may be a step closer, thanks to an array to test the conditions that lead to liver damage.

Shu Chien and colleagues at the University of California, San Diego, US, have demonstrated a system that can identify the biological components that lead to or alleviate liver disease. The array works by controlling the range of environments surrounding an array of star-shaped liver cells - hepatic stellate cells or HSCs. HSCs make up five to ten per cent of the liver and are normally in a resting state but when the liver is diseased, they begin to proliferate. This can lead to fibrosis, a build-up of connective tissue, which can impair the liver's function and cause cirrhosis.

Current approaches to identify the factors affecting HSC biology typically focus on each factor individually, ignoring the complex cross-talk between the many components acting on the cells. 'How these factors interact with each other to affect HSC activation remains unclear,' Chien explains. 'To overcome the shortcomings of traditional assays, we developed a system for the simultaneous screening of hundreds of physiochemical parameters on HSC behaviour.' By exposing cell arrays to different protein mixtures the system allows the researchers to rapidly identify the conditions that either promote HSC activation or maintain the resting state. 'We could systematically assess the complex relationships between the cells and their microenvironment,' says Chien. 

The array system determines which combinations of factors promote cell activation, and which do not

The US team found that certain proteins are critical in regulating HSC activation and that the proteins influence one another's action on the cells. 'In the future, such approaches will yield insight into the role of microenvironment components in vivo,' says Chien, 'and will lay the foundation for identifying more efficient antifibrotic therapies.'

Bill Murphy, of the University of Wisconsin-Madison, US, studies how environment affects stem cell behaviour. He says that Chien's work is 'an elegant example of the potential of array-based strategies in biology and medicine. Emerging approaches like this may ultimately lead to a more advanced understanding of natural microenvironments,' adds Murphy, 'as well as identification of new microenvironments that elicit specific cell behaviors, such as tissue regeneration.'

Michael Spencelayh

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