How to Make Stem Cells… Using Acid!

Just yesterday, two papers were published in the journal Nature showing a completely novel way to make stem cells – the approach uses an acid bath. This method is rather shocking in its simplicity, and it’s unclear why or how it works, but somehow it does. Basically, the researchers took adult (somatic) cells from young mice, temporarily exposed the cells to a low pH (an acid bath), and found that this rather quickly turned the cells into stem cells. The authors are calling them STAP cells, for stimulus-triggered aquisition of pluripotency.

As indicated by their name, the STAP cells specifically appear to be pluripotent, meaning they theoretically have the ability to turn into any cell type of the adult body. Pluripotent stem cells in general have great potential for making lab-grown tissues and organs needed in transplants. But while the creation of STAP cells is indeed exciting – and has many implications, such as potentially more readily enabling the cloning of animals – further studies need to be done to verify what exactly these cells are and what they can do.

How do the STAP cells fit in with the stem cells currently used in research labs? Human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) are different, commonly used pluripotent stem cells. hESCs are made from early-stage embryos (called blastocysts) while iPSCs can possible be made out of any cells from a person’s body – ones that may not be missed much, such as from blood or fat tissue samples. To make iPSCs, “normal” cells are forced to make certain proteins that are essential for the hESC identity. So, not only is it easier to get cells to make iPSCs, but iPSCs can also potentially be patient-specific, bypassing immune rejection problems that often arise with transplants. (And, just earlier this week it was announced that Advanced Cell Technology, the only US company with hESC clinical trials, is facing financial and legal difficulties, so hESCs aren’t looking so appealing these days.) Making iPSCs using human cells was first demonstrated in 2007, and the research community has made amazing progress since then.

Generally, genes are randomly inserted into cells to make them become iPSCs, which could be dangerous if the new genes ended up disrupting important genes already in the cells. The STAP cells have the advantage that they do not do this – the cells undergo a chemical treatment, but do not have their genetics directly manipulated. That said, just last summer researchers at Salk Institute for Biological Studies reported being able to turn cells into iPSCs using a mixture of chemicals instead of genes. So, ultimately, STAP cells might not really have an advantage in this respect afterall.

A concerning aspect of the STAP cells is that they use newborn, 1-week-old mice (the approach was much less successful with adult mice). iPSCs, on the other hand, can use fully mature animals. It’s possible that, with further study, researchers will be able to make STAP cells using older donor animals. This would definitely improve the feasibility of eventually using STAP cells to create patient-specific cells in humans.

That said, a potential advantage of the STAP cells is how efficient it is to make them – about 25% of the young mouse cells survive the stressful acid bath treatment, and 30% of those then become pluripotent cells. While this might seem low, it is a greater efficiency than is typically seen when making iPSCs (which convert about 1% of cells).

Overall, the STAP cells are indeed an exciting creation, but they need further characterization and possibly raise more questions than they answer. Why would cells respond to stress by becoming stem cell-like? Is this a natural coping mechanism you could find in the body? Can other stressful conditions work even better at inducing cells to become stem cells? And, of course, what other relatively simple methods are out there waiting to be discovered that could possibly replace more complex approaches we’re currently using?

For further reading:

• Haruko Obokata et al.’s article “Stimulus-triggered fate conversion of somatic cells into pluripotency” in Nature
• Haruko Obokata et ak.’s article “Bidirectional developmental potential in reprogrammed cells with acquired pluripotency” in Nature
• David Cyranoski’s article “Acid bath offers easy path to stem cells”
• Andrew Pollack’s article “Study Says New Method Could Be a Quicker Source of Stem Cells”
• Teisha J. Rowland’s post “Recent Breakthroughs with Induced Pluripotent Stem Cells”
• Teisha J. Rowland’s post “Reaching K-12: Stem Cell Awareness Day”
• Teisha J. Rowland’s other blog, All Things Stem Cell
• Teisha J. Rowland’s book Biology Bytes: Digestible Essays on Stem Cells and Modern Medicine