With the introduction of just four factors, researchers have successfully induced differentiated cells taken from mouse embryos or adult mice to behave like embryonic stem cells. The researchers reported their findings in an immediate early publication of the journal Cell.
The cells–which the researchers designate "induced pluripotent stem cells" (iPS)–exhibit the physical, growth, and genetic characteristics typical of embryonic stem cells, they reported. "Pluripotent" refers to the ability to differentiate into most other cell types.
"Human embryonic stem cells might be used to treat a host of diseases, such as Parkinson’s disease, spinal cord injury, and diabetes," said Shinya Yamanaka of Kyoto University in Japan. "However, there are ethical difficulties regarding the use of human embryos, as well as the problem of tissue rejection following transplantation into patients."
Those problems could be circumvented if pluripotent cells could be obtained directly from the patients’ own cells.
"We have demonstrated that pluripotent stem cells can be directly generated from fibroblast cultures by the addition of only a few defined factors," Yamanaka said. Fibroblasts make up structural fibers found in connective tissue.
Embryonic stem cells are derived from inner cells of the mammalian blastocyst, a ball of cells that develops after fertilization and goes on to form a developing embryo. Cells from other parts of the body can also be "reprogrammed" by transferring their nuclear contents into egg cell precursors called oocytes or by fusion with embryonic stem cells, earlier studies showed.
Those findings provided evidence that unfertilized eggs and embryonic stem cells contain factors that can confer pluripotency to differentiated cells, Yamanaka said.
"We hypothesized that the factors that play important roles in the maintenance of embryonic stem cell identity also play pivotal roles in the induction of pluripotency" in other body cells, he explained.
The researchers selected 24 genes–all previously found to play a role in early embryos and embryonic stem cell identity–as candidate factors that might give body cells the ability to become other cell types.
The researchers found that four of those factors, known as Oct3/4, Sox2, c-Myc, and Klf4, could lend differentiated fibroblast cells taken from embryonic or adult mice the pluripotency normally reserved for embryonic stem cells.
They further reported that transplantation of the iPS cells under the skin of mice resulted in tumors containing a variety of tissues representing the three primary types found in mammalian embryos. Those primary "germ layers" in embryos eventually give rise to all an animal’s tissues and organs.
