Exposure to acid turns adult cells into stem cells

A mouse embryo formed with specially treated cells from a newborn mouse that has been transformed into stem cells--Courtesy of Nature

An international team of scientists has found a new way to create stem cells without the use of an embryo or outside DNA--an advance in stem cell technology that doesn't carry the ethical concerns of embryonic stem cells or the safety issues of induced pluripotent stem cells.

Stem cells have been alluring to both scientists and the general public ever since their discovery opened up the possibility of treating countless diseases and other medical conditions. But despite huge advances in stem cell research in recent years, obstacles remain.

"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," said senior author Dr. Charles Vacanti, director of the Laboratory for Tissue Engineering and Regenerative Medicine at Brigham and Women's Hospital in Boston, in a press release.

Researchers at Brigham and Women's Hospital, Japan's Riken Center for Developmental Biology and Harvard University detailed their findings in the Jan. 30 issue of the journal Nature.

Harvesting embryonic stem cells, which are able to differentiate into any type of human cells and are thus highly useful, can cause the destruction of the embryo. Controversy surrounding producing embryonic stem cells has led to a greater research focus on induced pluripotent stem cells, first engineered by Shinya Yamanaka at Kyoto University in Japan in 2006. The original reprogramming method uses viruses to introduce the new DNA information into adult cells. Though iPS cells don't raise the same ethical concerns linked to the use of human embryonic stem cells, they pose their own set of problems. The viruses that enter the adult cells have the potential to introduce foreign DNA and spur the growth of tumors instead of helping to grow healthy tissue.

To create their new stem cells, researchers first tested mature adult cells in the lab, letting them multiply and stressing the cells close to death by exposing them to things like trauma, low oxygen levels and an acidic environment. Within a few days, the researchers discovered that the cells survived and recovered from the stressful stimulus by naturally reverting into a state that is equivalent to an embryonic stem cell. These embryonic-like cells 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.

Next, investigators tested their theory in mice that had been genetically altered with a specific mutation to light up green under a specific wavelength of light. Using an acid shock treatment, they stressed the green fluorescent protein (GFP+) cells in the blood. Days after exposure to the acidic environment, the blood cells reverted back to an embryonic stem cell-like state. These stem cells then began growing in spherical clusters. Scientists took these cell clusters and implanted them into normal mouse embryos that had not been genetically engineered or given the acid bath to create a mixture of cells. The implanted clusters spawned GFP+ tissues in all organs tested, confirming that the cells were pluripotent.

While there are still no FDA-approved therapies that use stem cells, the new research may give scientists a new way to engineer stem cell treatments for a variety of diseases and conditions using patients' own cells without the need for genetic manipulation.

- see the study abstract
- read the press release from Brigham and Women's Hospital