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 鈥渋ntelligent
surface鈥�, 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 鈥減ainting鈥� two layers of
cells onto a surface.
Another problem is that using artificial materials to support tissue can
trigger an immune reaction. 鈥淚nert materials aren鈥檛 inert enough,鈥� says David
Williams, an expert on implants at Liverpool University.
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Now Teruo Okano of the Tokyo Women鈥檚 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鈥攖he tricky part is removing the cells, because they stick to the
dish. 鈥淵ou normally use enzymes to separate the cells,鈥� Okano says. 鈥淏ut this
damages membranes and disrupts the function of cells.鈥� It also dissolves the
sheet into separate cells.
Okano鈥檚 trick is to coat the bottom of the dish with a temperature-responsive
polymer called poly-(N-isopropylacrylamide). At 37 掳C, the polymer
is water-repellent, which allows cells to bind to the surface. But when the
polymer is cooled below 32 掳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. 鈥淚t鈥檚 a superb example of how you can manipulate cells,鈥� 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鈥檛 help.
The layered structure seems to be crucial for their survival, he says. 鈥淲e
have been able to maintain function for 3 to 4 months,鈥� 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. 鈥淲e don鈥檛 know how
much we can layer,鈥� 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鈥檚 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.