Breakthrough in stem cell creation using acid bath

Behind the Headlines

Thursday January 30 2014

This method could lead to a quick and simple way of generating ‘personalised’ stem cells

This technique could help treat a range of illnesses

"Stem cell researchers are heralding a 'major scientific discovery'," BBC News reports.

Japanese scientists have created pluripotent stem cells (stem cells than can form all parts of the body) essentially by dipping mouse blood cells in acid, and then growing the cells in the presence of specific chemicals. If this could work in humans then it could have a range of intriguing applications.

There are currently only four established ways to obtain stem cells which can form all parts of the body:

  • from embryos
  • from unfertilised eggs
  • from embryo stem cells which have undergone modification in the laboratory
  • from a mature cell such as a skin cell, by reprogramming it with genes using a virus in the laboratory

These current techniques are lengthy and complex and using embryonic stem cells also raises ethical concerns.

This new technique may offer a much quicker, simpler and less ethically fraught method. The researchers found that after exposing blood cells from mice to a weak acid solution for 30 minutes, the cells were able to form different types of cells (they became pluripotent).

By growing these cells in the presence of specific chemicals, the researchers could also get the cells to ‘self-renew’ (divide and renew themselves for long periods). The ability to self-renew and to form different types of cells means that the cells had become stem cells.

It is not known why exposure to low pH should cause mature cells to gain the ability to form different types of cell under laboratory conditions. And so far the research has only been performed on cells from mice.

It should be noted that results were not as good when blood cells were taken from adult mice. This is exciting research but it is likely to be some time before the technique can be developed for use in humans.

 

Send in the clones?

If this technique could be scaled up to work in humans then, in theory, it could be possible to create a perfect human clone of yourself from one of your blood cells.

 

Such an experiment is unlikely to be performed, at least in the near future. It is likely to meet with considerable ethical opposition from both religious and medical groups, as well as many governments. And, novelty or shock value aside, it is difficult to see what would be the scientific benefit of such an experiment.

Where did the story come from?

The study was carried out by researchers from the RIKEN centre for Developmental biology, Kobe, Japan; Tokyo Women’s Medical School; Harvard Medical School, Boston and Irwin Army Community Hospital, Kansas.

It was funded by the Intramural RIKEN Research Budget, a Scientific Research in Priority Areas, the Network Project for Realization of Regenerative Medicine, and the Department of Anesthesiology, Perioperative and Pain Medicine at Brigham and Women’s Hospital.

The study was published in the peer-reviewed medical journal Nature.

Generally the media reporting of this study was accurate, although The Times incorrectly assumed that any weak acid would do – such as citric acid (lemon juice).

The researchers used a specific acid called “Hank’s balanced salt solution” (which was described as having a similar acidic (pH) level as Coca-Cola) in addition to numerous other chemicals under strict environmental conditions in the laboratory.

 

What kind of research was this?

This was a laboratory study which aimed to see if a mature cell (such as a white blood cell, or lymphocyte) could acquire the ability to produce many different types of cell after being exposed to a stress factor. Cells with the ability to produce many different types of cell are called “pluripotent”. A similar process is known to occur in plants after they are exposed to drastic environmental changes.

As this was a laboratory study and carried out in mice, it is not known whether the findings would be directly reproducible in humans.

 

What did the research involve?

The researchers took blood cells from the spleens of week old mice. They put them in a weak acid solution (pH 5.7) for 30 minutes at 37°C, and then put them into petri dishes and grew them at normal pH. The researchers repeated this process with blood cells from adult mice, and with cells from different parts of the body of week old mice (brain, skin, muscle, fat, bone marrow, lung and liver tissues).

The researchers called the cells they obtained from exposure to low pH “stimulus-triggered acquisition of pluripotency” or STAP cells.

The researchers did a number of experiments to characterise the STAP cells. They grew the cells in the laboratory and observed whether they had the ability to form different types of cell, and injected them into mice to see what would happen.

They injected STAP cells into mice embryos and then implanted them back into female mice. These cells were labelled so that the researchers could find out if they produced any cells in the growing embryo.

 

What were the basic results?

The researchers found that after the low pH treatment, blood cells lost features characteristic of blood cells and gained features characteristic of pluripotent cells.

These STAP cells could be obtained from adult blood cells (but fewer survived) and from other types of cell (collected from the brain, skin, muscle, fat, bone marrow, lung and liver tissues).

The STAP cells could form many types of tissue, both when grown in the laboratory and when injected into mice.

After being injected into early stage embryos, it was found that STAP cells could form all parts of baby mice, and could make the whole embryo. Mice made from a mixture of normal and STAP cells appeared to develop normally, and the STAP cells were also present in the offspring of these mice.

The researchers found that in addition to being able to make all the parts of the embryo, the STAP cells could also form the placenta.

The ability to form all parts of an embryo means that STAP cells are similar to embryonic stem cells. Embryonic stem cells make all cells in the body and can self-renew, which means that when they divide they form another copy of themselves.

STAP cells were different to embryonic stem cells in two key respects: they could not divide that many times, but they could form the placenta (which could be useful), whilst embryonic stem cells cannot.

The researchers carried out further experiments and found that by growing the cells in the presence of different chemicals they could get the STAP cells to self-renew, or in other words become STAP stem-cells.

 

How did the researchers interpret the results?

The researchers say, “This study has revealed that somatic cells latently possess a surprising plasticity. This dynamic plasticity – the ability to become pluripotent cells – emerges when cells are transiently exposed to strong stimuli that they would not normally experience in their living environments.”

They go on to say, “a remaining question is whether cellular reprogramming is initiated specifically by the low-pH treatment or also by some other types of sublethal stress such as physical damage, plasma membrane perforation, osmotic pressure shock, growth-factor deprivation, heat shock or high calcium exposure.”

 

Conclusion

This research has shown a new, simpler technique produced a type of stem cell from mature cells, though they have some differences from embryonic pluripotent stem cells.

The differences include that STAP cells are not able to self-renew unless they are grown in the presence of specific chemicals, and they are able to form the placenta in addition to all the different cell types making up the body. The implication of both differences is as yet unclear.

It is possible that in the future, stem cells created using this technique could be used to treat a wide range of illnesses.

An example cited by BBC News is age-related macular degeneration, an eye condition caused by damage to specialised cells inside the eyes. The technique could potentially be developed to generate cells to replace the damaged cells.

A limitation of the research, so far, seems to be the timing of when the cells can be collected. The results were best when blood cells were taken from one week old mice, but not very good when the samples were taken from adult mice. Hopefully this can be addressed through future research.

Longer studies will also need to be completed to find out if the cells act differently in the long run – for example, producing too many or too few cells and producing the right types of cells.

The researchers point out that they do not yet have the answer as to why the weak acid causes the cells to change but they are continuing their investigations.

Overall, this is an exciting piece of research that may have long-lasting implications on how stem cell research and therapy is carried out in the future. 

Analysis by Bazian. Edited by NHS Choices.

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Links to the headlines

Stem cell 'major discovery' claimed. BBC News, January 29 2014

Scientists use citric acid to create stem cell ‘game changer’. The Times, January 29 2014

'Stem cells' created in less than 30 minutes in 'groundbreaking' discovery. The Daily Telegraph, January 29 2014

Simple way to make stem cells in half an hour hailed as major discovery. The Guardian, January 29 2014

Stem cell power unleashed after 30 minute dip in acid. New Scientist, January 29 2014

Links to the science

Obokata H, Wakayama T, Sassi Y, et al. Stimulus-triggered fate conversion of somatic cells into pluripotency. Nature. Published online January 30 2014

Obokata H, Sassi Y, Niwa H, et al. Bidirectional developmental potential in reprogrammed cells with acquired pluripotency. Nature. Published online January 30 2014

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Analysis by Bazian

Edited by NHS Choices

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