ROME, February 3, 2011 ( – Are the new stem cell technologies too good to be true? New research suggests this may be the case.

Researchers at the Salk Institute for Biological Studies in La Jolla, California say they have found that induced pluripotent stem (iPS) cells may retain the genetic memory of their previous life, which could restrict the possible uses of such cells in therapy.

The study, published in this week’s online edition of the journal Nature, found significant differences between the reprogrammed iPS cells and true pluripotent embryonic stem cells.

In creating iPS cells, scientists take a mature cell, one that has already differentiated into a particular type of tissue, such as skin, and “unzip” it, turning off the genes that command it to be that particular type of cell. The hope is that this will create a cell that is as malleable as an embryonic stem cell, and can therefore be manipulated to become any type of tissue.

The researchers, however, found that the cells’ epigenomes – chemical markers attached to DNA that regulate the way genes are turned on and off – created large sections of difference between the iPS cells and embryonic pluripotent cells. Some of the iPS epigenomes had not reverted to the pluripotent state, but retained the “epigenetic memory” of their original state. When the researchers used the iPS cells to create mature cells in the lab, this memory persisted.

“This study definitively demonstrates that there are differences between the two cell types,” said Joseph Wu, a stem cell biologist at the Stanford University School of Medicine who was not involved in the research.

The team’s leader, Joseph Ecker, said the study examined 1.2 billion places in each genome where such chemical markers exist, making the study unusually thorough.

“Up to this point, people were looking through a keyhole,” he said. “We’re opening up the door.”

Wu said that this does not mean that iPS cells cannot be used in regenerative medicine. He said that scientists might find ways to harness the epigenetic memory to help treat disease. He gave the example of iPS cells created from heart cells that retain some of their cardiac characteristics.

“We need to do more research to see what exactly this means,” he said

In 2006, Japanese researcher Shinya Yamanaka of Kyoto University made headlines around the world when he announced the creation of iPS cells created from adult tissue that had the same properties as embryonic stem cells. The field of regenerative medicine has taken up iPS research as an ethical alternative to embryo research, which results in the deaths of millions of embryonic human beings.

The hope was that iPS cells would allow doctors to regenerate damaged tissue with new tissue that was a genetic match to the patient. But some are predicting that this latest discovery in how iPS cells work will be a set-back in the efforts to use them in regenerative medicine.

Kyoto University, however, is going forward and has announced that it has obtained the exclusive patent rights to the iPS technology.


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