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Stimulus‐triggered acquisition of pluripotency: Revolutionizing human disease modeling and regenerative therapies?

The recent report of the cellular reprogramming phenomenon “stimulus-triggered acquisition of pluripotency” (STAP) is a potential new breakthrough in stem cell research that may revolutionize the generation of “personalized” pluripotent stem cells. In 2006, somatic cells were reprogrammed for the first time into a pluripotent state by introducing a combination of four exogenous factors. The resulting induced pluripotent stem cells, capable of transforming into any tissue of the body, were the beginning of a new era in stem cell research, with a number of possible uses, ranging from cellular disease modeling to cell and tissue regenerative therapy. Reprogramming has been studied extensively since that time, but using transgenes or chemicals to initiate the process remained necessary. Obokata et al now describe a completely new way of reprogramming cells. They investigated the question of whether nuclear reprogramming into pluripotency can occur simply in response to a short exposure to external stimuli such as a low-pH stressor. For this, they isolated lymphocytes from postnatal mice that tested negative for pluripotent gene expression and performed a 30-minute treatment in pH 5.7 medium. After culturing these cells for 7 days, they identified STAP cells in selected cell clusters that demonstrated features of pluripotency. This included in vivo differentiation into all three germ layers; however, the cells showed a lack of self-renewal capacity. Subculturing the STAP cells for an additional 7 days in an adrenocorticotropic hormone–containing medium remarkably changed their proliferation to a level observed in embryonic stem cells, leading to the new term STAP stem cells. Assuming that STAP cells can possibly be derived from human somatic cells as easily as from mouse cells, this technique would highly facilitate the generation of pluripotent cells from individual patients. This is particularly relevant for diseases affecting tissues not accessible in vivo, such as the brain. The possibility of directly investigating the pathological properties of such disease-relevant cells may help reveal the pathogenesis of many diseases, including movement disorders. Given that STAP reprogramming is likely to be a short and inexpensive process, these cells hold great promise for the development of new treatment options. Importantly, the generation of STAP stem cells is independent of any chemical or genetic manipulation, rendering them particularly interesting for the development of regenerative therapies. Of note, this article has raised a vivid debate in the stem cell field regarding the reproducibility of these findings, accompanied by an investigation of the journal Nature (Nature; doi:10.1038/nature.2014.14738). Thus, it will be important to follow future experimental evidence related to this fascinating phenomenon.