Scientists Force Mature Cells to Revert to Stem Cells

Scientists have turned back the hands of time in cells within a living creature.

Researchers in Spain used a technique created seven years ago to force mature cells in mice to revert to an original form of stem cell with the potential to change into any type of living tissue. Previously, scientists were only been able to achieve this change in a petri dish.

The newest experiment, outlined today in the journal Nature, may one day let doctors work entirely inside the body to regenerate tissue and, perhaps, more complex organs, said George Daley, director of stem cell transplantation at Boston Children’s Hospital. This could include reconnecting a severed spinal cord or generating healthy heart cells.

“This is the next step along a continuum,” said Daley, a professor at Harvard Medical School in Boston who wrote an accompanying editorial on the work, which he wasn’t involved with. “What this is hinting at is that maybe we can, by regressing tissues in the patient, regenerate this embryonic potential and, with direction, regenerate a particular tissue.”

The reverted mouse cells were also found to be more primitive than stem cells taken from embryos or created in the lab. This means they can be turned into a placenta and other embryonic-support membranes, a factor beyond the capacity of the other cells, the researchers wrote.

The latest finding modifies a technique that won Shinya Yamanaka the Nobel Prize for medicine last year. Using mice whose genes could be manipulated at will, the scientists duplicated the factors Yamanaka had used to regress adult cells into stem cells. The cells that regressed in the dosed mice were in the stomach, the intestines, kidneys, and pancreas.

‘Surprising’ Finding

“You don’t need the milieu of the petri dish,” Daley said in a telephone interview. “You can just do this right in the tissues. That’s surprising.”

In today’s report, some of the mice had tumors that developed in embryonic support structures as well as a yolk sac, suggesting they were more primitive and powerful than other stem cells, the scientists wrote.

“These embryo-like structures are a reflection of going back to a more-primitive state,” Daley said. “That’s honestly what blew me away about the paper.”

It’s not clear why the cells developed in live mice are more powerful than those developed in petri dishes, said Maria Abad, a study author and researcher at the Spanish National Cancer Research Center in Madrid. Those grown in live bodies are more malleable, and behave differently when transplanted into a petri dish, she said.

The group is analyzing the outcome to see what may account for the differences, she said.

Safety Concerns

The finding also raises safety concerns for trials that use stem cells created in the laboratory, said Hongjun Song, the director of the stem cell program at the Institute of Cell Engineering at Johns Hopkins University in Baltimore.

Many of these cells are induced by adding four genes permanently to their DNA. That was a lesser safety concern before scientists demonstrated that it was possible to revert cells in living creatures, Song said.

Now that scientists know it’s possible to create stem cells in live animals using those four genes, it may mean that the techniques that permanently add those genes could increase the risk of tumors called teratomas, which are made of up of varying kinds of tissue that don’t belong where they develop.

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