Lymphocytes exposed to low-pH conditions are reprogrammed to a pluripotent state within 3 days. GFP shows expression of pluripotency marker Oct4, which is activated within about 2 days.
Note: The study covered in this article has been withdrawn due to substantial doubt about its findings.
In 2006, a team of Japanese researchers showed that terminally-differentiated adult somatic cells could be reprogrammed into pluripotent stem cells using genetic factors, to take on an embryonic state and able to differentiate into the full spectrum of bodily tissues. A flurry of research followed, and the therapeutic potential for tissue engineering of these reprogrammed cells, called induced pluripotent stem cells (iPSCs), are now undergoing evaluation through clinical trials. The difficulties of obtaining iPSCs are the low efficacy of reprogramming the cells, and the costs and time involved in their creation. A team of researchers at the Brigham and Women’s Hospital (as it happens, led by the same investigator who engineered the “earmouse” in 1997) collaborating with a team from the RIKEN Center for Developmental Biology (Kobe, Japan) have now discovered that mouse cells can be reprogrammed without direct genetic modification, and can be influenced simply by exposing them to a stressful environment for a few days.
By isolating white blood cells and exposing them to an acidic condition (pH ~5.6), the team was able to stimulate the cells into reprogramming into a pluripotent state – similar to embryonic stem cells, but without having to create an embryo. Furthermore, they hypothesized and showed that other stressors, such as trituration and perforation, were able to induce similar behaviors in the white blood cells. They coined these new cells as “stimulus-triggered activation of pluripotency” (STAP) cells. The discovery is surprising, and the researchers mused on some food for thought at the end of their report:
Why, and for what purpose, do somatic cells latently possess this self-driven ability for nuclear reprogramming, which emerges only after sublethal stimulation, and how, then, is this reprogramming mechanism normally suppressed? Furthermore, why isn’t teratoma (or pluripotent cell mass) formation normally seen in in vivo tissues that may receive strong environmental stress?
The team has shown that these cells are capable of self-renewal, that they differentiate into multiple lineages, and contribute to growing a normal mouse embryo. If future experiments go well and the technique is applicable to human cells, obtaining autologous pluripotent stem cells could one day be as easy as drawing blood.
Paper in Nature: Stimulus-triggered fate conversion of somatic cells into pluripotency
Note: The study covered in this article has been withdrawn due to substantial doubt about its findings.