Sep. 4, 1998 COLUMBUS, Ohio -- Ohio State University researchers have invented a device that grows human tumor cells in an artificial medium in order to produce a protein for possible cancer treatment.
The device, called a fibrous-bed bioreactor (FBB), is capable of growing cells for a variety of applications including fermentation, animal cell culture, tissue engineering, and waste water treatment. Researchers have shown that the FBB is able to produce large quantities of a protein -- Developmental Endothelial Locus-1 Protein, or Del-1 -- for cancer research.
Shang-Tian Yang, professor of chemical engineering, designed the bioreactor as a three-dimensional alternative to the flat dishes that scientists normally use to culture cells. Yang and two of his graduate students, Chunnuan Chen and Yu Liang Huang, presented the results of this work August 26 at the 216th national meeting of the American Chemical Society in Boston.
The FBB contains a forest of microscopic polyester fibers that anchor living cells in place. As the cells grow and reproduce, they wrap around the fibers as they would strands of protein in the body.
Other fibrous bioreactors exist, but Yang explained that the FBB possesses unique characteristics that overcome the disadvantages associated with them. For instance, if the fibrous material is too dense, it can strangle the cells. For that reason, the Ohio State researchers pack the Dacron fibers loosely inside the container to leave room for gas to circulate in interior channels. A flood of nutrients washes through the fibers to provide nourishment to the cells, while at the same time whisking away dead cells so they don’t clog the channels.
“The porous fabric provides a very high surface area for the cells to anchor on in three-dimensional space,” said Yang. “But the major difference is that other bioreactors try to contain the cells inside the fibers, so over time the cells become overcrowded and die. This new design allows cells to proliferate in three dimensions and grow naturally.”
The Ohio State researchers conducted this work in concert with scientists from Progenitor Inc., a biotechnology company in Menlo Park, Calif.
Progenitor commissioned Yang, Chen, and Huang to produce large quantities of Del-1 protein for clinical trial. The company provided the researchers with cells of human osteosarcoma, the most common malignant bone tumor, which it had genetically altered to produce Del-1.
Del-1 is useful to cancer researchers because it controls the development of blood vessels that feed nutrients to solid tumors. A drug based on Del-1 might cut off a tumor’s blood supply.
“We intensified our production of Del-1 by conducting it in a small reactor and automating it so we could run the reactor continuously for four months. Because of the special design of the bioreactor, cells can maintain their productivity for a long time,” said Yang.
The FBB saved the researchers a great deal of time and labor. Even though the device contains less than one liter of material, it sustained a volume of osteosarcoma cells roughly equal to that of 300 standard flat culture dishes.
Moreover, a conventional cell culture system produces about one million cells per cubic milliliter, while in this experiment the FBB produced 500 million -- about half the density of normal human tissue.
Yang said that the FBB’s ability to produce high cell densities lends the device to the possible growth of replacement human organs such as artificial skin. He explained that the researchers would have to find a biodegradable fiber to substitute for the polyester, but the process would still work.
The researchers have patented the FBB and are now looking into new applications for it.
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