Until now, the existing technique for genetically reprogramming adult cells and converting them into stem cells required time — roughly several weeks — and had a dismal success rate of about one percent. Today, a team of Japanese scientists have published their research supporting a much simpler method, referred to as stimulus-triggered acquisition of pluripotency (STAP), which is more efficient, more rapid, and more successful than the existing technique. In fact, the new method, tested within mice, requires only that blood cells be dipped into an acid bath as a way of exposing them to a low pH.
Despite the seeming ease of this groundbreaking technique, the development process took years — nearly five — since Haruko Obokata, a stem cell biologist at the RIKEN Center for Developmental Biology in Kobe, Japan, first came up with the initial idea. One reason such a long delay spread between conception and birth was the fact that she needed to fully convince her scientific colleagues of the value of her technique. But that, as they say, is science.
Stem cells are unspecialized cells that have the remarkable ability to turn into any cell in the human body and for this reason they are a significant area of research for scientists seeking to develop personalized medicine. The technique of genetically reprogramming cells and creating stem cells, known as induced pluripotent stem cells (iPSC), was first reported in 2006 and demonstrated in human cells one year later. Since then, iPSCs have been very useful to scientists in drug development and modeling of diseases, though the process of creating these cells, which took and was not often successful, left much to be desired.
How, then, did the new STAP cell technique come about? One day while culturing cells, Obokata saw how some cells, after being squeezed through a capillary tube, shrunk to a similar size as stem cells. She wondered: Could simply stressing cells make them pluripotent? To investigate, she began a series of experiments where she applied different kinds of stress, including heat, starvation, and a high-calcium environment. Soon, she found that three stressors — perforating the cell membrane with a bacterial toxin, physical squeezing, and exposing a cell to low pH — induced signs of pluripotency in the cells.
Having made this significant discovery, Obokata next had to prove these cells were indeed capable of turning into any and all cell types in the manner of a true stem cell. To accomplish this, she turned to mouse-cloning pioneer Teruhiko Wakayama at the University of Yamanashi, Japan, who helped her by developing mice into which she could introduce her STAP cells. Next, she worked in the laboratory of Charles Vacanti, a tissue engineer at Harvard University. With his help, Obokata uncovered a biological explanation for her method: that generation of cells in this manner occurs in nature as a response to injury.
Today, Obokata has already genetically reprogrammed a dozen cell types, including those from different organs in the body. Although she believes the STAP method does not work on all cell types, it works with most and, on average, 25 percent of the cells survive the stress and 30 percent of those convert to pluripotent cells. Her research appears in two papers published simultaneously in Nature, along with an editor’s summary stating, “Extensive analysis of the molecular features and developmental potential of STAP cells suggests that they represent a unique state of pluripotency — and provide an alternative source of pluripotent cells…”
Obokata H, Wakayama T, Sasai Y, Kojima K, Vacanti MP, et al. Stimulus-triggered fate conversion of somatic cells into pluripotency. Nature. 2014.
Obokata H, Wakayama T, Sasai Y, Niwa H, Kadota M, Takata N, et al. Bidirectional developmental potential in reprogrammed cells with acquired pluripotency. Nature. 2014.