PARIS – Scientists in Spain say they have succeeded in making mature cells in living mice revert to their youthful, versatile state — a step toward the goal of regenerating tissue by using stem cells.
Right now, the technique is at its earliest stage and is hedged with safety questions, which makes it impossible to envisage in humans.
But, said the researchers, it opens up a new strategy leading to a beguiling end: that one day damaged tissue will be healed by simply reprogramming nearby adult cells into replacements for the lost or diseased area. A transplant would not be needed.
Stem cells have spurred huge interest in medical research worldwide. They are immature cells that differentiate into the specialized cells that make up various tissues and maintain the human body.
In 2006, a team led by Shinya Yamanaka in Japan announced a breakthrough: A clutch of four genes that had been introduced into adult cells in a lab dish prompted these cells to revert back to their baby state.
These so-called induced pluripotent stem cells — known by the acronym iPS — have since become the most closely followed innovation in the field.
Despite many hurdles, they are seen by some as being even more promising than embryonic stem cells, the “gold standard” for versatility but a source that is hotly opposed by moral conservatives.
Reporting in the scientific journal Nature, a team led by Manuel Serrano and Maria Abad of the Spanish National Cancer Research Center (CNIO) created genetically modified mice that carried the four “Yamanaka genes.” The genes were then switched on by administering a drug in the mice’s water.
Cells in the rodents’ kidney, stomach, intestine and pancreas all showed signs of being reprogrammed, back to an extremely versatile or “totipotent” state that seemed more like embryonic stem cells than lab-dish iPS cells, the team reported.
The technique confirms that reprogramming can be done in living tissue, and not just in the lab dish, said Serrano.
“We can now start to think about methods for inducing regeneration locally and in a transitory manner for a particular damaged area,” he said.
Other researchers were divided as to whether the work is a game-changer, and all cautioned that daunting obstacles lie ahead.
There was no evidence of what happened to the cells in the mice after they had been reprogrammed.
In addition, the animals developed clusters of tumors called teratomas, although this had been expected as part of the research. Creating teratomas is a benchmark of the versatility of an experimental stem cell.
“This paper is very exciting. Clearly, nobody wishes to do this for therapeutic purposes because this leads to the formation of tumors,” Ilaria Bellantuono, a University of Sheffield researcher, told the Science Media Center, a not-for-profit organization in London.
“However, this is a proof of concept that pluripotency can be achieved in vivo,” or in living animals.
The process “still needs these iPS cells to be safely converted to useful ‘adult’ cells in the body,” warned Chris Mason, a professor of regenerative medicine at University College London.
“The major challenge will be tightly controlling every step in this potential approach in order to deliver clinical benefits whilst avoiding significant complications.”