A simple recipe - including just four ingredients - can transform adult human skin cells into cells that resemble embryonic stem cells, researchers report in an immediate early publication of the journal Cell, a publication of Cell Press.
The converted cells have many of the physical, growth and genetic features typically found in embryonic stem cells and can differentiate to produce other tissue types, including neurons and heart tissue, according to the researchers.
They added, however, that a comprehensive screen of the activity of more than 30,000 genes showed that the so-called “induced pluripotent stem (iPS) cells” are similar, not identical, to embryonic stem cells. "Pluripotent" refers to the ability to differentiate into most other cell types.
The chemical cocktail used in the new study is identical to one the team showed could produce iPS cells from adult mouse cells in another Cell report last year. That came as a surprise, said Shinya Yamanaka of Kyoto University in Japan, because human embryonic stem cells differ from those in mice. Those differences had led them to suspect "that some other factors might be required to generate human iPS cells,” he said.
The findings are an important step forward in the quest for embryonic stem cell-like cells that might sidestep the ethical stumbling blocks of stem cells obtained from human embryos. He emphasized, however, that it would be “premature to conclude that iPS cells can replace embryonic stem cells.”
Embryonic stem cells, derived from the inner cell mass of mammalian blastocysts--balls of cells that develop after fertilization and go on to form a developing embryo--have the ability to grow indefinitely while maintaining pluripotency, the researchers explained. Those properties have led to expectations that human embryonic stem cells might have many scientific and clinical applications, most notably the potential to treat patients with various diseases and injuries, such as juvenile diabetes and spinal cord injury.
The use of human embryos, however, faces ethical controversies that hinder the applications of human embryonic stem cells, they continued. In addition, it is difficult to generate patient or disease-specific embryonic stem cells, which are required for their effective application. One way to circumvent these issues is to induce pluripotent status in other cells of the body by direct reprogramming, Yamanaka said.
Last year, his team found that four 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. Fibroblasts make up structural fibers found in connective tissue. Those four factors are “transcripton factors,” meaning that they control the activity of other genes. They were also known to play a role in early embryos and embryonic stem cell identity.