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Feb 27, 2014
 |  BC Innovations  |  Tools & Techniques

(Pluri)potent acid

Academics and companies alike are scrambling-and thus far failing-to reproduce a surprisingly simple method for generating pluripotent mouse stem cells that uses an external stress stimulus to trigger reprogramming. Whether the method simply does not work or just faces initial hurdles similar to those experienced by other induced pluripotent stem cell-generating technologies remains to be seen.

If it does work, the technique offers minimal invasiveness without the need for genetic reprogramming factors, nuclear transfer or small molecules.

A team from the Brigham and Women's Hospital and RIKEN Center for Developmental Biology reported the generation of pluripotent mouse stem cells by simply exposing somatic cells to low pH.1

The state of the art for making induced pluripotent stem (iPS) cells is to introduce pluripotency-promoting genetic elements or combinations of small molecules into differentiated cells.2,3 In both cases, the transition to iPS cells takes at least two weeks.

The group, led by Charles Vacanti, took genetic manipulation out of the equation and sped up culture times. Based on observations that differentiated plant cells can revert to a stem cell state under stress,4 the group hypothesized that a similar phenomenon could occur in differentiated animal cells.

The researchers started with hematopoietic cells from newborn mice carrying an Oct4-GFP reporter transgene and monitored its expression following different stresses. Oct4 is of one of the core pluripotency factors.

The most effective stressor turned out to be an acidic environment. Mouse hematopoietic cells that were shocked for 30 minutes by low pH and then cultured in neutral medium needed only 7 days to reprogram and activate Oct4-GFP.

Other pluripotency markers also were induced, suggesting that the hematopoietic cells had indeed reverted to an embryonic stem cell (ESC)-like state. The group named the resulting cells stimulus-triggered acquisition of pluripotency (STAP) cells.

In vitro differentiation and in vivo teratoma formation assays showed that STAP cells gave rise to...

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