Reprogrammed Adult Cells Not an Alternative to Embryonic Stem Cells

Cells refashioned into stem cells remember their origin, two studies suggest

July 20, 2010— -- Adult tissues that are reprogrammed to become stem cells may not be the blank slate that researchers find in other stem cell types, further questioning whether adult cells can be considered a reliable alternative for embryonic stem cells, according to a two new studies published Monday in Nature and Nature Biotechnology.

In one study, researchers at Children's Hospital in Boston, genetically engineered adult tissues in mice to imitate embryonic stem cells. They found these reprogrammed cells, known as induced pluripotent stem cells, meant to act as blank cells, actually retained characteristics of the tissue that it once was.

"We're finding that there's a subtle memory of where the [adult] cells came from," said Dr. George Daley, director of the stem cell transplantation program at Children's Hospital and lead researcher of one of the studies.

Stem cells are heralded as a tabula rasa that can be fashioned into healthy organs and other tissues to potentially treat diseases. Adult cells are often used to reproduce cells of its origin, while embryonic stem cells are not limited to a specific tissue type.

However, both studies suggest that induced pluripotent stem cells made from reprogrammed adult cells may not be equivalent to embryonic stem cells, as many researchers once thought.

"We thought we could reset [blood cells] so we can make a bone tissue or other tissue types, and realized it not make a bone tissue as well. But it did well going back to a blood cell," said Daley.

Researchers currently use adult stem cells to treat genetic diseases. For example, adult blood cells are used to treat genetic blood diseases such as leukemia, and skin cells may be used to regenerate skin tissue and heal otherwise fatal wounds.

"It's an advantage when you want to make the same tissue type, but not if you're looking at making something new," said Daley.

While induced pluripotent stem cells are not yet used in practice, researchers are exploring ways that any adult cell can be reprogrammed into stem cells and refashioned into any type of tissue in the body, regardless of where it was originally taken.

According to Ihor Lemischka, director of the Black Family Stem Cell Institute at Mount Sinai School of Medicine, these studies suggest that induced pluripotent stem cells may more likely resemble adult tissue cells rather than embryonic stem cells.

"If you make an IPS cell from skin cells and you want to use that for studying blood diseases, then we know now that you might be better off starting with blood tissue instead," said Lemischka.

Furthering the Argument for Continued Stem Cell Research

While the ethical debate rages over whether reprogrammed stem cells may effectively substitute for embryonic stem cells, many experts said the studies released Monday confirm that each cell type, adult or embryonic, should not be considered interchangeable.

"The take home message is that what stem cell biologist have been arguing for years is true -- that we need to continue studying both stem cells, because we don't know which cells can be used for which applications," said Sean Morrison, director of the Center for Stem Cell Biology at the University of Michigan.

Although Daley's research suggested that cells refashioned into pluripotent stem cells still remember its original tissue structure, Morrison said these cells could still be useful for other types of therapies besides ones that need embryonic stem cells or adult tissue cells.

"In the end, adult stem cells will probably prove superior for certain therapeutic applications, reprogrammed cells might work for other applications, and embryonic cells for others," said Morrisson.

While some studies suggest that each stem cell type contains unique features that are not identical to another type, Morrison said many similarities and differences of each stem cell type are not well understood.

"These are some of the first studies to suggest that there really are important differences," said Morrison.

Lemischka said understanding the comparative features of each type of stem cell will help researchers find the potential benefits of all.

"The main impact of IPS technology will be to develop reliable and robust ways to model and study disease," said Lemischka. "And that will lead to making suitable cell populations to study drugs that hopefully will [treat diseases]."

But to do that, Daley said it is important to continue researching embryonic stem cells to find how to better manipulate induced pluripotent stem cells.

"It's at great risk to the progress of the field, to ignore the lessons that embryonic stem cells still have to teach us," said Daley.