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Breakthrough: Scientists create embryonic stem cells without embryos

Jan 30th 2014 at 8:37 PM

Researchers from Brigham and Women's Hospital, in collaboration with researchers from Japan, have discovered a way of changing adult stem cells back to their original embryonic state by exposing them to low oxygen and acidic environments. This is according to a study recently published in the journal Nature.

The research team, including senior author Dr. Charles Vacanti of Brigham and Women's Hospital, says their findings may one day lead to the creation of embryonic stem cells specific to each individual without the need for genetic manipulation.

Human embryonic stem cells are pluripotent, meaning they can change into many different cell types in the body.

Stem cells have already been used for the treatment of many health conditions. Last year, Medical News Today reported on a study revealing that scientists had grown artificial skin from stem cells of the umbilical cord.

Other research has detailed the use of stem cells for the treatment of cardiovascular disease, brain disorders and blood diseases.

Stem cell research has raised ethical concerns in the past, as extracting human embryonic stem cells from a 4- or 5-day-old embryo can lead to its destruction.

In 2006, scientists created induced pluripotent stem cells (iPS) - an alternative to harvesting embryonic stem cells. This involves changing an adult stem cell back to its pluripotent state by genetically manipulating the cells with DNA.

The majority of scientists now use iPS for research. However, unlike human embryonic stem cells that are able to grow into any type of mature cell, adult cells can only grow into specific types of cell, so their use is limited.
Mature adult cells exposed to different environments to reach embryonic state

The research team was inspired by the ability of a plant callus - a collection of plant cells that grow into a new plant after being injured on an existing plant.

The investigators thought this process could apply to mature adult stem cells. They hypothesized that once an adult stem cell had turned into a certain cell type, it could be forced to change again through a natural process.

With this in mind, the researchers exposed multiple mature adult stem cells to traumatic, low oxygen and acidic environments until they had almost died.

They found that within a few days, these mature cells survived and changed into a state equivalent to that of an embryonic stem cell.

Commenting on these findings, Dr. Vacanti says:

"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."

Pluripotent stem cell tissue growth in mice

Using mature blood cells from green fluorescent protein-transgenic (GFP+) mice (genetically modified mice who light up green under certain wavelengths of light), the researchers exposed the cells to an acidic environment.

They found that in a few days, these blood cells also changed back to a state similar to that of an embryonic stem cell and started to grow in clusters.
Stem cells
Researchers found that by exposing mature adult stem cells to stressful outside environments, they were able to revert back to their original embryonic state.

These clusters were added to the embryo of mice who were not genetically modified in order to create a "chimera" - a mix of cells.

The investigators found that the cell clusters caused GFP+ tissues to grow in all organs of the mice that were tested. This confirmed that the cells were pluripotent.

The researchers say their findings suggest that by exposing mature adults cells to stressful external environments, this could release them from the environment they are used to and cause them to change back to their original state.

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

The research team says that if a skin biopsy or blood sample from humans could show a similar process, then this could lead to the creation of person-specific embryonic stem cells.

These stem cells could then be used to create tissue without adding any outside genetic material into the cells. The researchers note that this could provide countless treatment options for patients.

But for now, the research team plans to further investigate the mechanisms in which mature adult stem cells revert back to a pluripotent state.

Haruko Obokata, of the Brigham and Women's Hospital and first author of the study, adds:

"If we can work out the mechanisms by which differentiation states are maintained and lost, it could open up a wide range of possibilities for new research and applications using living cells.

But for me, the most interesting questions will be the ones that let us gain a deeper understanding of the basic principles at work in these phenomena."

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