Liver on a plate

Artificial organs could be built layer by layer using a non-stick dish

Michael Le Page New Scientist 7apr01

TISSUES that mimic the complex cellular structure of organs such as the liver have been made by researchers in Japan. With the help of an "intelligent surface", they can build up layer after layer of different cells. They claim the technique could revolutionise tissue engineering.

Shaped tissues such as the famous ear grown on the back of a mouse can be made by seeding a moulded scaffold material with cells. Recreating the complex arrangements of different cell types found in many tissues is much more difficult, though researchers have made bladders by "painting" two layers of cells onto a surface.

Another problem is that using artificial materials to support tissue can trigger an immune reaction. "Inert materials aren't inert enough," says David Williams, an expert on implants at Liverpool University.

Now Teruo Okano of the Tokyo Women's Medical University has developed a way to create layers of different cell types without using any artificial support. He starts by growing a single layer of cells in a flat dish. This is easy--the tricky part is removing the cells, because they stick to the dish. "You normally use enzymes to separate the cells," Okano says.

"But this damages membranes and disrupts the function of cells." It also dissolves the sheet into separate cells. Okano's trick is to coat the bottom of the dish with a temperature-responsive polymer called poly-(N-isopropylacrylamide). At 37 °C, the polymer is water-repellent, which allows cells to bind to the surface. But when the polymer is cooled below 32 °C for a few minutes, it becomes hydrophilic, and the cells lose their grip. Crucially, the one-cell-thick sheets remain intact when they detach. The sheets can then be stacked up to form more complex structures. Okano has mimicked the structure of the liver with alternating sheets of hepatocytes and endothelial cells. "It's a superb example of how you can manipulate cells," says Williams.

Many researchers are trying to grow hepatocytes in culture, with the aim of creating artificial livers that could keep patients with acute liver failure alive for the few days it takes their livers to recover. Cultures of hepatocytes only survive for 5 or 6 days without endothelial cells, and simply mixing them up randomly with endothelial cells doesn't help. The layered structure seems to be crucial for their survival, he says. "We have been able to maintain function for 3 to 4 months," he told a conference on medical technology at Imperial College in London last week.

So far his team has made tissues up to five layers thick. "We don't know how much we can layer," he says. The researchers have implanted the engineered liver tissues into mice to see if the endothelial cells can form capillaries. If the tissues can develop a blood supply, it might be possible to make much thicker structures using the technique. Okano's team has also created layers of heart muscle cells from chicks. He hopes such tissue could help heart-attack patients. The team is also trying to make more complex structures such as tubes.

source: http://www.newscientist.com/newsletter/news.jsp?id=ns228545