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Tuesday, March 18, 2008

A machine that churns out three-dimensional artificial tumours could help improve anti-cancer drug

A growth solution flows past traps adding new cells to each growing tumour
A machine that churns out three-dimensional artificial tumours could help improve anti-cancer drug testing, researchers say. The "tumour factory" offers a better alternative to the flat cultured cells currently used to test new anticancer drugs.
"Cells grown in a monolayer are very useful in many studies," says Maria Teresa Santini of the Istituto Superiore di Sanità in Rome, Italy, who was not involved with the work . "But they cannot represent a three-dimensional tumour."
In a real cancer, different parts of a tumour are fed different amounts of oxygen. Cells growing in a flat monolayer all receive the same amounts of oxygen are all exposed to an equal quantities of nutrients. "Testing anticancer drugs on these models may be very inaccurate," Teresa says.
Small clumps of cells known as 3D tumour spheroids provide a better model. But, until now, spheroids have had to be made one at a time in a process that produces different sizes each time.
Luke Lee's group at the University of California in Berkeley, US, has developed a technique to quickly generate spheroids of a standard size at low cost. The breast cancer drug Taxol has already been shown half as effective on spheroids as it is on 2D cell cultures.
Breaking the mouldAt the heart of the Berkeley team's device is an array of U-shaped traps each 35 micrometers across and 50 micrometers deep, which are made from polydimethylsiloxane (PDMS), a silicon-based organic polymer.
The array is held inside a chamber through which flows breast cancer cells suspended in growth solution. Cells that flow into the microscopic traps cannot flow out again, although the growth solution can escape from a small gap underneath the trap too large for a cell.
Over the course of a few hours, empty traps become filled with cells and, over about 7 hours, they attach to one another and form tumour spheroids containing 9-11 cells inside each trap. Solution constantly supplies the outer layer of the spheroids with fresh nutrients and oxygen, and removes waste excretions. The PDMS polymer also allows oxygen to reach the cells.
"The continuous flow in our device plays an important role in spheroid formation since it helps maintain the cells in a compact group," says Lee. "The cells have more chance to contact each other and adhere."
Mass productionSantini is impressed by Lee's study. "This represents an important development," she told New Scientist. "It's been difficult forming spheroids of the same characteristics before – having same size spheroids makes the tumour response to a particular concentration [of drug] more statistically relevant, since it can be repeated without error due to cell number."
But Wolfgang Mueller Klieser of Johannes Gutenberg University in Mainz, Germany, is not convinced that growing uniform spheroids is necessary because collections of mismatched ones can quickly be sorted by size. "But, one great advantage here is that they can produce spheroids relatively rapidly – the standard methods take 10 days to produce spheroids 0.5 mm across."
Lee's spheroids are ten times smaller than that, points out Helene Bobichon of the University of Reims, France. "Making spheroids with a too low a number of cells could be inefficient for getting similar results to an "in vivo" response," she says.
Lee says small spheroids less accurately represent tumours at an earlier stage of development, and has plans to make larger ones using new prototypes of the device. "We focused on small spheroids for the proof of concept," he says,

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