Scientists discover new way to make stem cells - just add acid!

30 January 2014
Stimulus-Triggered Acquisition of Pluripotency (STAP) cells [RIKEN Center for Developmental Biology]


Published in Nature today, Japanese and US scientists have reported a new way to make stem cells. This new method relies on the use of acid to turn white blood cells and other body cells into pluripotent stem cells and represents a possible simpler and cheaper way to obtain stem cells. 

Australian researchers have made the following comments about this discovery:

Professor Martin Pera is Program Head of Stem Cells Australia and Chair of Stem Cell Sciences at the University of Melbourne
“These ground-breaking studies report some truly remarkable results. The authors show that by subjecting cells from many tissues of the body to sub-lethal stress, such as a brief exposure to an acidic environment, it is possible to reprogram the cells back to the pluripotent embryonic state in which they have the ability to give rise to any type of tissue. Thus for example, a brief acid shock enables the generation of brain cells from skin cells. This type of reprogramming has previously only been achieved either through cloning, or through forced overexpression of embryonic genes in adult cells. The findings reported in Nature are remarkable because the reprogramming stimuli the authors describe are so simple and so effective at resetting the controls that govern cell behaviour. The authors did a thorough job of demonstrating that their reprogrammed cells had the properties of embryonic stem cells.
The study provides a new approach for the generation of pluripotent stem cells from adult tissue.  If these findings in mice can be duplicated with human cells, the technique will provide us with the simple and straightforward means yet devised for generating stem cells that can be used to study and treat disease. Of course, if the technique does work with human cells, it will also be necessary to show that stem cells made in this fashion are as safe and effective in producing cells for transplantation as stem cells from embryos."

Professor Nadia Rosenthal is Founding Director of the Australian Regenerative Medicine Institute, Monash University
“The reprogramming of adult cells to a stem cell or pluripotent state, which won the Nobel Prize for Medicine last year, has heretofore required invasive genetic manipulation. By contrast, the current reports have shown that newborn mouse blood cells can be reprogrammed to achieve pluripotency merely by changing their environmental conditions in tissue culture, and that the resulting cells acquire a broader spectrum of embryonic characteristics than normally achieved with genetic techniques.
This stimulus-triggered acquisition of pluripotency, or "STAP", has profound implications both for our basic understanding of embryonic development and for therapeutic interventions in regenerative medicine if it proves broadly applicable to adult cells, and can be used to reprogram human cells as well as those from mice.”

Associate Professor Ernst Wolvetang is Group leader of the Stem Cell Engineering Group at the University of Queensland
“The ability to generate stem cells that can go on to become any type of tissue from mature mouse cells by simply increasing the acidity of their surroundings for about half an hour, followed by relatively straightforward cell culture steps, will make ’re-setting’ adult cells to create stem cells more mainstream and more accessible. In particular,  the short timeframe required to produce these type of cells as compared to previously available methods, and the fact that there is no need to manipulate genes suggests this  method has great potential for regenerative medicine applications, provided efficiency can be improved in adult cells and that the method is transferrable to human cells.
The study certainly  challenges the accepted view that the barriers to changing which genes are switched on and off in mature mammalian cells are considerable and resistant to change.
Most convincingly, they show that this new type of stem cell can be passed on through the generations, one of the most stringent tests of whether they are truly potent stem cells. Perhaps mammalian cells under laboratory conditions can be convinced to behave  more like newts and axolotls (species that can regenerate limbs or organs following severe injury) than we appreciated.
As a note of caution, since the mechanism underlying stress induced reprogramming of the cells remains enigmatic at this point in time, it will be important that other laboratories replicate these data independently to confirm these results.”

Dr Jose Polo is  Group Leader of the Department of Anatomy and Developmental Biology at the Australian Regenerative Medicine Institute, Monash University
“In 1958, John Gurdon demonstrated that a mature cell had in its nucleus all the information necessary to create a whole organism. In 2006, almost 50 years later, Shinya Yamanaka found the way to control this information using four transcription factors (proteins that control which genes are being read) and rocked the scientific world with the generation of iPS cells. For Gurdon and Yamanaka the iPS cells meant a Nobel Prize, for the rest of the humanity the potential use in cell-replacement therapies and modelling ofhuman diseases. 
Today, just eight years after Yamanaka, the laboratories of Vacanti and Wakayama demonstrated that a simple external stimulus applied at the right time, such as an increase in acidity, is enough to trigger a cell identity conversion into STAP cells. These cells present an extraordinary cellular plasticity, as iPS cells they can give rise to the whole organism, however STAP cells can give rise to the placenta as well. The work was done in mice, however the iPS history will predict that it will work in humans as well. 
How easy, robust and safe the method is, only time and more research can say. In the meantime, the regenerative and reproductive field have a new tool and can start thinking about new applications. One major question arising from the work is why normal adult cells in the body, which are exposed to stressful stimuli similar to those described in this study under a range of circumstances, do not undergo the same reprogramming back to the embryonic state. This type of plasticity would have dire consequences if there were not powerful restrictions in the tissues of the body to prevent it happening.  If this reprogramming happened under normal circumstances, tissues of the body that normally are exposed acidic conditions, such as the lining of the stomach, could develop into disorganised tumours containing a bizarre range of cell types. Thus, the work raises profound questions about how cells behave under conditions of stress. The answers to these questions will yield profound new insights into cell regulation in health and disease.”

Dr Carmel O'Brien is a Research Scientist & Team Leader, Laslett Stem Cell Group, CSIRO Materials and Science Engineering and has an adjunct appointment at the Australian Regenerative Medicine Institute, Monash University
This research demonstrates the ability to send adult mouse cells back to an embryonic state in a culture dish, simply by subjecting the cells to an acidic environment.  This is a remarkable finding that not only avoids the use of embryos to create pluripotent cells that are capable of forming potentially all adult cell types, but has also been achieved without the introduction of any external DNA. The process of producing these cells, termed STAP cells (stimulus-triggered acquisition of pluripotency), is a potential game-changer for future cell-based therapeutic treatments.  If the same process demonstrated by the RIKEN/Brigham and Women’s Hospital researchers can be reproduced for human adult cell types, researchers may be able to create patient-specific cells from skin or blood samples, without the introduction of external genetic material. 
Going forward, it will be very interesting and important to understand the mechanisms by which the fate of an adult cell can be changed by external stress cues.  For STAP  cells and their derivative tissues to potentially translate to human therapies, it will be critical to develop a sophisticated understanding of the genetic mechanisms at play and to ensure that such cells are genetically stable for safe use in transplantation.

For more information see:
Cyranoski, D. Acid bath offers easy path to stem cells. Nature (29 January 2014).
Obokata, H. et alNature 505, 641–647 (2014).
Obokata, H. et alNature 505, 676–680 (2014).

Media coverage:
Stem cell find hailed as revolutionary THE AUSTRALIAN (30 January 2014)
Scientists hail stem cell 'breakthrough' ABC Radio AM (30 January 2014)
Stem cell 'major discovery' claimed BBC News (29 January 2014)