Safer Stem Cells?

Recent efforts by researchers at the WiCell Research Institute may just have put the lid back on the controversy over whether scientists should generate new human embryonic stem (ES) cell lines.

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MADISON, Wis.—Recent efforts by researchers at the WiCell Research Institute may just have put the lid back on the controversy over whether scientists should generate new human embryonic stem (ES) cell lines. Senior scientist Dr. Ren-He Xu and colleagues have found a way to replace the animal feeder cells traditionally used to grow human ES cells with a fully synthetic mixture of proteins and buffers. The findings suggest that it might be possible to "clean up" existing cell lines, removing the contaminants that complicate their use in basic research and the development of cell-based therapeutics.
Although the new method will not provide immediate benefits, it provides hope that scientists will eventually test a wider array of therapeutics in the clinical setting. If true, this effort will have a significant financial impact as a recent report by London-based market research company Vision-gain suggests that the stem cell and tissue engineering market will exceed $10 billion within the next decade.
Says Dr. Xu: "With completely animal-free systems coming into being and other cell-therapy hurdles removed, there will be increasing demand to derive new and safe human ES cell lines to save the lives of desperate patients with Parkinson's, diabetes, spinal cord injuries, bone marrow deficiencies, and other conditions."
The current problem, as Xu explains it, is that human ES cells have traditionally been derived and cultured on mouse embryonic fibroblasts as feeder cells, or in medium conditioned by the feeder cells. Either condition contains unknown factors secreted by the feeder cells, some of which are required for self-renewal of ES cells.
Most of these factors, however, are unwanted or may even be dangerous as they may transfer animal pathogens to the ES cells and then to patients who receive the stem cell-based therapies.
Unfortunately, researchers can't simply eliminate the feeder cells or feeder cell-conditioned medium, because the ES cells will simply differentiate to other cell types. Thus, researchers like Xu had to determine what essential molecules secreted by feeder cells to maintain ES cell in an undifferentiated state and how to remove animal cells or animal materials from the ES cell culture.
In a paper published in the journal Nature Methods (February 17), Xu describes a refined medium system he developed that removes the need to grow ES cells on feeder cells by using two synthetic engineered proteins that promote growth but inhibit differentiation.
"The new medium makes the ES cells safer for their potential use to treat patients and makes the culture of human ES cells much easier and cheaper," Xu says. "By eliminating the feeder cells, drug screening or other research on human ES cells will be easier and more straightforward, without uncertain background interference and potential contamination by the feeder cells."
Unfortunately, the feeder cells aren't the only potential source of contamination. "Traditionally, Invitrogen's Matrigel is used as the coating matrix, which is extracted from mouse tumor cells," he says. "My new system eliminated the feeder cells, but it still needs Matrigel to coat the culture dish."
Xu is confident that this and the development of a cocktail of completely defined materials to replace the medium will be solved.
"By then, it will be time to completely clean up existing human ES cell lines and derive new lines that are animal-free and safe to treat patients," he says.

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