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Stem Cell Breakthrough May Lead to MS Treatments
Date:4/9/2009

t if they added one of two proteins, FGF2 or SHH, to the cells' growth media, they could reliably induce those cells to become oligodendrocytes. The human application was obvious: ESC-derived oligodendrocytes could either be used directly as a cell therapy for MS and related diseases, or serve as research tools to study them.

But, when Dr. Su-Chun Zhang of the University of Wisconsin, Madison, who has been studying oligodendrocytes and myelination for nearly a quarter-century, tried to apply the culture conditions painstakingly worked out in rodents to human cells, oligodendrocytes failed to emerge.

"When we expand these [rodent] progenitor cells with FGF2 (and another factor called PDGF), these progenitor cells will become oligodendrocytes," Zhang said. But, "What we discovered was that when we did [the experiment] in the same way with human progenitor cells, they were blocked in this process."

By carefully dissecting the molecular events that occur as human ESCs differentiate first into neural stem cells, then neural progenitor cells, then pre-oligodendrocytes, and finally mature oligodendrocytes, Zhang and his team identified the source of the difference: While both rodents and humans control the process with the same regulatory circuitry and use the same molecules (including both FGF2 and SHH), FGF2 behaves differently in each species.

In mice, FGF2 promotes oligodendrocyte maturation; in humans, it inhibits the process.

"This finding is actually quite significant scientifically," said Zhang, "because even [though] the transcriptional network is more or less the same, yet they respond to the same factor in an opposite way. To me, that's quite extraordinary."

Once that simple fact was understood, the experiment could be tweaked so that human embryonic stem cells could, in fact, generate oligodendrocytes.

The study, said Coetzee, "just reinforces the absolute importance of being able to do
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