Japanese-Led Team Develops Way to "Reset" Mature Cells to Pluripotent Cells

Kobe, Jan. 29 (Jiji Press)--A Japanese-led team has developed a novel way to "reset" mature mouse cells to a pluripotent state, from which they can develop into various tissue again, the team said in the British journal Nature. The team, led by Haruko Obokata of the Kobe, Hyogo Prefecture-based Riken Center for Developmental Biology, succeeded in reprogramming mouse blood and skin cells to the pluripotent state by exposing the cells to stresses such as dipping them into a mildly acidic solution. The new method enables quicker and more efficient production of pluripotent cells than the technique to produce induced pluripotent stem (iPS) cells invented by Kyoto University Prof. Shinya Yamanaka. His technique involves nucleus manipulations, namely injections of certain genes into target cells. The new method "is totally different" from the technique to produce iPS cells, Obokata, 30, said, adding that her team's method, if it can be applied to human cells, "would not only contribute to regenerative medicine but also help break new ground in medicine." The team's finding also shattered the commonly accepted theory that it is impossible to reset cells that have fully developed into blood, muscles or other tissue by exposing them to external stimuli alone. The cells produced under the new method were named stimulus-triggered acquisition of pluripotency (STAP) cells. The team collected lymphocytes, a type of blood cells, from the spleens of one-week-old mice. The cells were cultured after being dipped for about half an hour in a solution with a pH, a measure of acidity, of 5.7. In culture with a special solution, pluripotent cell-specific genes, such as Oct4, used to produce iPS cells, began to grow active in surviving cells in a week, meaning the cells were turned into STAP cells, the team said. Obokata and her colleagues confirmed STAP cells' ability to develop into any tissue, as mice that received STAP cell-injected embryos gave birth to chimera babies. They also found the premature cells can contribute to the formation of the placenta in the experiment. Furthermore, the team successfully converted STAP cells into highly proliferative stem cells, though the stem cells were found to have lost ability to develop into placental tissues. Also according to the discovery of the team, success rates to make STAP cells ranged from 7 to 9 pct, higher than those for iPS cells. The STAP cell production periods were two to three weeks shorter than those required for making iPS cells. In addition, unlike iPS cells, none of the STAP cells turned cancerous, the team said. STAP cells can be made from skin and muscle cells, not only from blood cells. As well as immersion into a mildly acidic solution, such stresses as the passage of cells through glass tubes and exposure to a mildly toxic substance were found to be effective for their production. The team believes that external stimuli help change how some genes in the cells work, although it is uncertain how such a change occurs. "I am proud that such important research results have been released by Japanese researchers," iPS cell inventor Yamanaka said. "I hope that pluripotent cells will be made from human cells under the same method." END