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New stem cell production technique comes as a shock

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February 3, 2014

Mouse embryo generated from STAP cells (Image: Riken)

Mouse embryo generated from STAP cells (Image: Riken)

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An international research effort has found that mature animal cells can be shocked into an embryonic state simply by soaking them in acid or putting them under physical stress. The fortuitous breakthrough could prove to be massive for many fields of medical research if the method can be replicated using human cells, something researchers are confident will be possible.

The collaboration between Harvard-affiliated Brigham and Women’s Hospital (BWH) and the Riken Center for Developmental Biology in Japan found that by bathing mature cells harvested from mice in a weak acid, they reverted to a stem cell-like pluripotent state. Pluripotency, as the name suggests, is when a cell has the potential to become one of the many different cells found in an animal; "pluri" refers to many, as in plural, and "potent" – the potential to become that many.

Pluripotent cells are an important resource for many forms of medical research. Embryonic stem cells (ESCs) are one type of pluripotent cell, yet the harvesting of ESCs has its opposition, as it involves the destruction of human embryos. Successful attempts at creating stem cells culminated in the 2012 Nobel Prize-winning research in which Shinya Yamanaka produced Induced Pluripotent Stem Cells (iPSC) from mature cells by introducing several pieces of DNA. The new technique being pioneered by researchers at Harvard and Riken is much simpler and would greatly reduce the expense of stem cell production.

“It may not be necessary to create an embryo to acquire embryonic stem cells. Our research findings demonstrate that creation of an autologous pluripotent stem cell, a stem cell from an individual that has the potential to be used for a therapeutic purpose without an embryo, is possible,” said senior author Dr. Charles Vacanti, chairman of the Department of Anesthesiology, Perioperative and Pain Medicine and director of the Laboratory for Tissue Engineering and Regenerative Medicine at BWH.

The origins of the research date back to 2001 and can be credited to Dr. Vacanti, a BWH anaesthesiologist best known for his work on the “earmouse” which gained notoriety in 1995. In 2001, Dr. Vacanti was working towards finding new cell types able to be used in his tissue engineering research. During this study he mistakenly reported a new type of stem cell he called “spore-like cells," by passing neural stem cells and mature tissue cells through ever-smaller pipettes. He believed that these spore-like cells existed in all tissue, and that they remained dormant until needed to repair tissue damage. After heavy peer criticism, the research was shelved.

Six years on, enter Japanese graduate student Haruko Obokata. Armed with new insight, Dr. Vacanti and Obokata started investigating if the harsh process of extraction had produced the stem cells rather than his previous belief that they had been isolated from the tissue mixture. This new line of inquiry led the researchers to a remarkable finding, namely that any mature adult (somatic) cell has the potential to turn pluripotent if subjected to sub-lethal stress such as mild acidity, high or low temperature, or mechanical force. They named the process stimulus-triggered acquisition of pluripotency (STAP). It can be seen taking place in the following video.

Mature blood cells taken from a live donor and engineered to glow were treated with a mild acid. These decreased in size and lost their functional characteristics during the process of conversion from mature somatic cell to STAP cell. The glowing STAP cells were then introduced to a (non-glowing) mouse blastocyst and were shown to contribute 100 percent to the somatic tissue in the embryo that formed. This was easily seen, as the embryo indeed glowed.

“It’s exciting to think about the new possibilities these findings open up, not only in areas like regenerative medicine, but perhaps in the study of cellular senescence and cancer as well. But the greatest challenge for me going forward will be to dig deeper into the underlying mechanisms, so that we can gain a deeper understanding of how differentiated cells can covert to such an extraordinarily pluripotent state,” Obokata said.

The research was published in the journal Nature. The glowing mouse embryo can be seen in the video below.

Sources: Brigham and Women’s Hospital (BWH), Riken Center for Developmental Biology

12 Comments

Good.

Inject a mild acid into a cancerous tumor then zap it.

After the body has re-metabolized some of the converted cells repeat the process until the tumor is all gone.

Nairda
3rd February, 2014 @ 08:14 pm PST

What happens when cells are subject to metabolic acidosis, and stressed with heat, cold, or a mechanical stimulus, such as ultrasound?

Jon Catling
4th February, 2014 @ 07:05 am PST

This would be a good occasion to revisit the work of an engineer who tried to work out an application of RFI to kill cancer. He was strongly motivated by the progressing cancer that did eventually kill him but nonetheless, his attempts showed great promise. This may well be a very useful tool to combine with other tools that independently are an incomplete therapy.

StWils
4th February, 2014 @ 08:42 am PST

It will be interesting to see if they can get such an embryo to term and then grow into a healthy adult. The concern with these stem cell reversions is that they remain stable in their new differentiated form and are not more liable to become tumours.

DomainRider
4th February, 2014 @ 09:43 am PST

Who would have thought it was as simple as putting cells in acid or heating / cooling them?

OTOH Sounds too obvious to be true.

sidmehta
4th February, 2014 @ 10:31 am PST

As is always the case with a major break through, Dr. Vacanti might have paved the way, but the idea of soaking in acid came from Dr. Obokata. There is no doubt it is a joint collaboration, but he should not try to take the main credit when it belongs to her.

Her first article was rejected by Nature by a reviewing scientist with reknowned credential to be too simplistic to the point of ridiculing the existing, extremely costly and intricate processes other researchers have been engaging in.

If this can be replicated with human cells, it will make the pluripotent cells so inexpensive, the researchers who were after gold mines may be disappointed.

kamaaina
4th February, 2014 @ 11:17 am PST

Very impressive breakthrough indeed. In error though is the quote: "the harvesting of ESCs has its opposition, as it involves the destruction of human embryos" Dr. Robert Lanza MD has produced ESC lines from embryos without any destruction and is indeed using them routinely for human regenerative procedures. These true ESC's, I suggest, will be much more active and functionally focused than converted adult cells.

Willsonx
4th February, 2014 @ 06:55 pm PST

For those of us with spinal and spinal cord and nerve damage any of these stem cell breakthroughs are hope. Even if it does not happen soon enough to help me it would be great if my daughter did not have to suffer all her life like I have since 1973. Since a night in the Winter in early 1973 I have been in pain every minute of every day and after three episodes of "broken backs" resulting in 8 compressed verts and one burst fracture and all that goes with it stem cells are our best hope.

My problem stems from osteoporosis and a much too adventuresome life style. It was only in my late forties we found I was in the lowest 1% of men my age for bone density and by then most of the damage was done. Now it is trying not to fall and things like drugs to help with the bone density but the only hope for the pain is a combination of pain meds.

Three different orthopedic surgeons, very good ones, have told me they are amazed I still walk. Still if there could be a way to help it would be great. Last night NPTV Universe with Stephen Hawking had a show on the same general subject of stem cells and at the end he lamented that it is too late for him. I am 10-12 years younger but it is probably too late for me too but if they want to try some out I would be first in line.

vblancer
4th February, 2014 @ 11:03 pm PST

Mechanical stress or shock is a common event in the life of many cells; it must take rather more than that to stimulate pluripotency. Unless that's a regular stage in tissue repair.

Brian Hall
5th February, 2014 @ 09:56 am PST

The real issue(s) surrounding stem cells is: money! Will people with neuro issues- such as sci (since 1961)- really be allowed to utilize functional improvement/pain/etc. Treatment from stem cells, or will health insurance and big pharma weild the real power and keep it on the shelf?!

Folks need to "rise up" and demand immediate usage right now!, as we have been "g pigs" for years for drugs, etc.

Researchers know that the stem cells work, or the little hope on dr. Hawkings' stem cells program on the science channel would have been put off.

Way too many of us are not in the 'miracle cure' mode, but functional improvement is a whole solid ball of wax that needs to come out now!

JP
5th February, 2014 @ 11:31 am PST

Think this is great, but wonder why stress or shock doesn't cause cells to revert to a stem cell-like pluripotent state? Now we're told stress is bad for US. Would love to try stem cell therapy, sooner than later if only I could afford it or be a test candidate.

Daruma
6th February, 2014 @ 08:57 am PST

@Wilsonx:

While I strongly doubt harmless harvesting of ESCells is possible as you claim (How are these human embryos implanted back after harvesting? Has any of them grown to maturity?) there is another drawback to ESCs, which should give pause even to those that ignore the moral issue.

ES cells come from a different individual, and are not a genetic/immune match for the recipient. Any treatment with ESCs requires long-term immunosuppressants to be successful. The technique described here activates the subject's own cells, providing an autologous transplant without such problems.

Freederick
6th February, 2014 @ 06:13 pm PST
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