
Researchers are a step closer to creating patient-specific stem cells without the use viruses or foreign genes that could pose a cancer risk. A new study finds that a cocktail of two chemicals and a single gene is enough to convert some human cells into induced pluripotent stem (iPS) cells, potentially capable of making any other tissue in the body.
The new approach, published online today in Cell Stem Cell, is the latest tweak on a technique for creating human iPS cells by treating human cells with viruses that insert genes encoding OCT4, SOX2, KLF4 and C-MYC. The combination is known as Yamanaka factors, after Shinya Yamanka the Japanese scientist whose team helped develop the protocol.
Since then, teams all over the world have come up with dozens of tweaks, many focused on doing away with gene-inserting viruses that could cause cancer by disrupting tumour-protecting genes. Some protocols did away with C-MYC, a gene known to promote cancer. A paper published earlier this year swapped out genes for chemically modified RNA transcripts of the Yamanka factors.
But many scientists think that the safest way to make human iPS cells is to get rid of genes altogether and use chemicals to reprogram cells. In 2008, Sheng Ding’s team at the Scripps Research Institute in San Diego, California showed that a cocktail of one drug and two genes, OCT4 and KLF4 could reprogram neural stem cells, which already express other genes needed to make iPS cells.
Now, Ding’s team has created human iPS cells from skin cells by treating them with two chemicals and a single gene – OCT4. The resulting iPS cells look similar to embryonic stem cells and they express the same genes as iPS cells made through conventional approaches.
“This is indeed an interesting and important drug cocktail,” says George Daley, a stem cell biologist at Children’s Hospital in Boston. “There are clear strategies for replacing the Oct4 transgene with non-transgenic approaches, so we will have a couple of different ways to generate transgene-free cells. Very exciting indeed.”
Image of human embryonic stem cells courtesy of Wikimedia Commons