Researchers create embryonic stem cells without embryo

Transplant tissue: Stem cells in 'revolutionary' boost
Stress-treated lymphocytes expressed pluripotency marker Oct4. Right: STAP cells. Credit: Haruko Obokata

( —Since the discovery of human embryonic stem cells, scientists have had high hopes for their use in treating a wider variety of diseases because they are pluripotent, which means they are capable of differentiating into one of many cell types in the body.

However, the acquisition of from an embryo can cause the destruction of the embryo, thus raising ethical concerns. In 2006, researchers introduced an alternative to harvesting embryonic called induced pluripotent stem (iPS) cells. They provided evidence that it was possible to send a normal adult cell back to an undifferentiated, state by introducing genetic material ("outside" DNA) into the cell, a process that alters the original state of the cell. To avoid the use of embryonic stem cells, other researchers have focused more on the use of , but the use is of these cells is limited because unlike embryonic stem cells that grow into any type of mature cell, adult stem cells can only grow into certain cell types.

Now, researchers from Brigham and Women's Hospital (BWH), in collaboration with the RIKEN Center for Developmental Biology in Japan, have demonstrated that any mature adult cell (a "somatic" cell) has the potential to turn into the equivalent of an embryonic stem cell. Published in the January 30, 2014 issue of Nature, researchers demonstrate in a preclinical model, a novel and unique way that cells can be reprogrammed, a phenomenon they call stimulus-triggered acquisition of pluripotency (STAP). Importantly, this process does not require the introduction of new outside DNA, the process commonly used to induce back into a state of pluripotentency.

"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. The fate of adult cells can be drastically converted by exposing mature cells to an external stress or injury. This finding has the potential to reduce the need to utilize both embryonic stem cells and DNA-manipulated iPS cells," said senior author Charles Vacanti, MD, chairman of the Department of Anesthesiology, Perioperative and Pain Medicine and Director of the Laboratory for Tissue Engineering and Regenerative Medicine at BWH and senior author of the study. "This study would not have been possible without the significant international collaboration between BWH and the RIKEN Center," he added.

Transplant tissue: Stem cells in 'revolutionary' boost
STAP cells generated entire fetus body. Credit: Haruko Obokata

Researchers, drawing from the ability of a plant callus – a node of plant cells that is created by injuring an existing plant, to grow into a new plant – hypothesized that any mature adult cell, once differentiated into a specific cell type, could be de-differentiated through a natural process that does not require inserting genetic material into the cells.

"Could simple injury cause mature, adult cells to turn into stem cells that could in turn develop into any cell type?" hypothesized the Vacanti brothers.

Beginning with mature adult cells, researchers let them multiply. After stressing the cells almost to the point of death by exposing them to various stressful environments including trauma, a low oxygen environments and an acidic environment, researchers discovered that within a period of only a few days, the cells survived and recovered from the stressful stimulus by naturally reverting into a state that is equivalent to an embryonic stem cell. The stem cells created by exposure to the external stimuli were then able to redifferentiate and mature into any type of cell and grow into any type of tissue, depending on the environment into which they were placed.

STAP cell conversion from lymphocytes. Credit: Haruko Obokata

To examine the growth potential of these cells, researchers used mature blood cells from GFP+ mice, mice that had been genetically altered with a specific mutation to light up green under a specific wavelength of light. They stressed the GFP+ cells from the blood by exposing them to an acidic environment and found that in the days following the stress, those cells reverted back to an embryonic stem cell-like state. These stem cells then began growing in spherical clusters, similar to a plant callus. The cell clusters were introduced into the developing embryo of a non-GFP mouse (whose cells do not light up green) to create a mixture of cells (a "chimera"). The implanted clusters were able to create GFP+ tissues in all organs tested, confirming that the cells are pluripotent.

Researchers hypothesize that these findings raise the possibility that unknown cellular functions that are activated through external stress, may set mature adult free from their current commitment and permit them to revert to their naïve cell state.

Mouse embryo with beating heart generated totally from STAP cells. Credit: Haruko Obokata

"Our findings suggest that somehow, through part of a natural repair process, turn off some of the epigenetic controls that inhibit expression of certain nuclear genes that result in differentiation," said Vacanti.

Researchers note that the next step is to explore this process in more sophisticated mammals and ultimately in humans.

If this same process can be demonstrated in , then some day, through a skin biopsy or blood sample, without the need for genetic manipulation,, researchers may be able to create specific to each individual, which in turn could be used to create tissue without the need to insert any outside genetic material into that cell, creating endless possibilities for therapeutic options.

Researchers write that further questions exist; Vacanti and colleagues are interested in exploring why and how stressful stimuli drive reprogramming to create the pluripotent state.

Explore further

New method increases supply of embryonic stem cells

More information: Paper: Stimulus-triggered fate conversion of somatic cells into pluripotency, … ull/nature12968.html
Journal information: Nature

Citation: Researchers create embryonic stem cells without embryo (2014, January 29) retrieved 16 October 2019 from
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User comments

Jan 29, 2014
Now What?
Fools were licking ESChasses!

Jan 29, 2014
It is now important to find more about Neoteny with this additional larvae of Axolotl.

Jan 29, 2014
Cluster of cells from W.B.C that was implanted into a mouse uterus developed into a Fetus.

Jan 29, 2014
Cluster of cells from W.B.C that was implanted into a mouse uterus developed into a Fetus.

He created "STAP Cells" from Human Skin cells also; But it must be replicated & Peer reviewed to be considered valid

Jan 29, 2014
Small correction in the sentence:
It is now important to find more about Regeneration with this additional Axolotl larvae.

i.e in Larvae of Salamanders

Jan 29, 2014
Cluster of cells from W.B.C that was implanted into a mouse uterus developed into a Fetus.

The Title of the Article with slight change is
"Stem cell discovery could Eliminate need for Embryos for Research & usher in Human Cloning"

Jan 30, 2014
How about putting a Mammoth cell to this kind of physical conditions?
Are those Cells beyond Recovery?

Feb 02, 2014
This is no wheres close to as revolutionary as it sounds. We routinely create stem cells from adult somatic cells without embryos for research purposes in labs throughout the planet since the publication of the Nobel prize winning paper by Takahashi et al in 2006. A great example of this is in the study of schizophrenia where we take adult fibroblasts from patients, reprogram them into human induced pluripotent stem cells (hiPSCs) and through multiple steps of differentiation, produce heterogeneous cultures of terminally differentiated neurons (http://www.ncbi.n...172000). This sums up the main problems in the clinical application of hiPSCs: producing homologous cultures, i.e. a single cell type, ensuring all cells have differentiated, and all differentiated cells closely match their in vivo counterparts. None of which has been further elucidated in this paper. Of course, this is still important but the hype is only partially warranted.

Feb 02, 2014
Here is a link to some stem cells I have been trying to produce over the last 7 months or so from immortalized human trophoblasts (HTR8), When cultured on non-adherent plates, like bacterial plates, they form aggregates called embryoid bodies, which I show in the above pictures, although the pictures show them after i have isolated them and cultured them on adherent plates. I am currently in the process of characterizing them but they were produced via similar methods to the above paper. Basically, you just treat your cells like crap: leave them in horrible conditions like low pH, grow to confluency (completely cover the plate with cells all touching each other), adding old media with low nutrients and pro-apoptotic factors, etc.

So you can see this isnt as amazing as it sounds, labs have probably accidentally been producing stem cells in cultures that are forgotten and just bleached without a second thought.

Feb 02, 2014
I guess I forgot to continue my original statement. I dont remember the year exactly but i think it was in 2008 when we tried to use hiPSCs in a clinical setting. The result was this, the majority of cells differentiate and only partially represent their in vivo counterparts. The remaining minority of cells were either partially or completely undifferentiated upon injection which then went on to produce aggregates of undifferentiated, fast proliferating, pluripotent cells. These may then produce tumors.

It wasn't until 2013 that we found that it takes 2-3 months AFTER reprogramming for a true resemblance to appear. We determine this mostly through methylation (Me) status of specific promoters. When the hiPSCs Me status resembles in vivo embryonic cells, we would say that these cells have more or less completely reprogrammed. Of course this is only tentative and no one would say we know with 99.9% certainty that we have truly produced full wildtype embryonic cells.

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