Creating lab tests that do without animals

Chang Ai-lien Straits Times 17 Mar 13;

In a move that could help do away with lab tests on animals, researchers here have successfully coaxed blank-slate human embryonic stem cells to transform into kidney cells, and engineered artificial human liver tissue from scratch.

Potential drugs can be tested for toxicity on such materials, which promises to be faster and more accurate than current methods.

"As such technology becomes more widely used, we will be able to replace and cut down on animal testing with these cheaper and more humane methods," said Professor Jackie Ying, executive director of the Institute of Bioengineering and Nanotechnology (IBN), which led the effort.

Both the liver and kidney remove poisons from the body, so drug companies use them as an early warning of whether a new compound could have toxic side effects.

Creating the tissue called for a suite of engineering and biological feats, ranging from creating the cells and developing the optimal way of feeding them, to giving them the perfect home to grow and miniaturising the testing process so only a tiny amount of cells and drugs are needed.

"We've worked through every aspect of the process and now we're putting all the pieces together to give companies the tools they need to produce new drugs faster and more cheaply," said Prof Ying.

The artificial liver piece, for instance, is grown on a plant-based material that encourages liver cells to assemble spontaneously.

Said IBN group leader Hanry Yu: "We engineered the environment to make the cells happy, mimicking the blood flow of the body and providing a porous and soft material that the cells can fit into.

"They behave very differently in a three-dimensional world like the human body, compared to the two dimensions of a petri dish."

In the case of the kidney cells, human embryonic stem cells - the unprogrammed cells that can transform into any cell the body needs - were coaxed into turning into specific kidney cells that play an important role in drug processing, said IBN principal research scientist Daniele Zink.

Since embryonic stem cells can grow indefinitely in cell culture, the source of kidney cells needed is potentially unlimited, she said.

While groups all over the world are generating specific cell types from embryonic stem cells, producing kidney cells has been particularly problematic, noted Professor Frank Bonner, the chief executive of Stem Cells for Safer Medicines, a not-for-profit company comprising British-based academic groups.

Calling the work a significant contribution to a complex and challenging area, the toxicologist added: "Many drugs are known to produce toxic effects in the kidney which can result in drugs failing in development or unexpected adverse reactions occurring in patients.

"The methods developed at IBN may potentially lead to the development of novel and improved drug screening tools."

The institute recently received a grant from the Agency for Science, Technology and Research to further their work, which is being done with the Experimental Therapeutics Centre, the Bioinformatics Institute and the National University Health System.

Big pharma has also come calling.

IBN is already working with the likes of Janssen Pharmaceuticals, a pharmaceutical company of Johnson & Johnson, and global health-care company Hoffmann La-Roche to commercialise its work.