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Scientists get closer to making safe patient-specific stem cells

October 8, 2009 |  9:00 am

Scientists are a big step closer to their long-term of goal of creating patient-specific stem cells that are safe to use and don’t require the destruction of embryos.

Induced pluripotent stem cells – also known as iPS cells – are all the rage in the nascent field of regenerative medicine. Like embryonic stem cells, they have the potential to become any type of cell in the body and could be used to grow replacement parts, such as insulin-producing beta cells for diabetes patients or nerve cells for repairing spinal cord injuries.

Eggan Even better, they can be made by reprogramming skin or other cells from the patients who need them. That not only eliminates the need to use embryos, it ensures that the replacement tissues made from iPS cells are genetically matched to patients and won’t be rejected by the body’s immune system.

But there’s still a big catch: In order to rewind adult cells to a pluripotent state, researchers have to turn on a set of dormant genes that have the potential to cause tumors. So do the viruses they use to activate those genes.

So researchers have been looking for ways around this problem. One approach is to snip out the genes and viruses once the reprogramming is complete. Another is to use DNA sequences called transposons in place of viruses, then delete the transposons after they’re no longer needed. One group of researchers has even used genetic engineering to modify the key genes so that they can enter the skin cells without requiring viruses or transposons.

But many scientists think the safest approach is to replace the genes altogether with so-called small molecules. In a study published online today in the journal Cell Stem Cell, researchers from the Harvard Stem Cell Institute report that a single compound they dubbed RepSox can replace two of the four key reprogramming genes.

“We’re halfway home, and remarkably we got halfway home with just one chemical,” senior author Kevin Eggan, a professor in Harvard’s department of stem cell and regenerative biology, said in a statement.

Eggan’s team identified RepSox by screening 200 compounds and waiting a couple of weeks to see which of them did the best job of transforming mouse cells into iPS cells in combination with three of the four reprogramming genes. The researchers were surprised to find that their compound not only replaced the gene Sox2 (hence the name RepSox), but also made the gene c-Myc obsolete.

Now the group will turn its attention to finding other small molecules that could replace the remaining genes – Oct4 and Klf4 – as well, “opening a route to purely chemical programming,” they write.

-- Karen Kaplan

Photo: Harvard stem cell scientist Kevin Eggan. Credit: Justin Ide / Harvard News Office

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