Wednesday, Oct 01, 2014

A paradigm changer?

New York Times | Posted: February 8, 2014 11:24 pm

ANDREW POLLACK

A study has found that a simple acid bath might turn cells in the body into stem cells that could one day be used for tissue repair and other medical treatments. The technique, performed only with cells from mice, might turn out to be a quicker and easier source of multipurpose stem cells than methods now in use.

“If reproducible in humans, this could be a paradigm changer,” said Dr Robert Lanza, chief scientific officer of the biotechnology company Advanced Cell Technology, who was not involved in the work. The new technique was developed by researchers at the Riken Centre for Developmental Biology in Kobe, Japan, and at Brigham and Women’s Hospital and Harvard Medical School in Boston. Two papers by the researchers were published recently in the journal Nature.

Dr Charles A Vacanti, director of the laboratories for tissue engineering and regenerative medicine at Brigham and an author of the studies, said the technique could also raise ethical issues, because it might provide an easier way than current cloning techniques of creating a duplicate of an animal, or even a person.

Some experts expressed caution, saying that more needed to be known about the new approach and that existing techniques for making stem cells had improved markedly in recent years.“The existing methods are already quite advanced,” said Sheng Ding, a scientist at the University of California, San Francisco, and the affiliated Gladstone Institutes. “It’s too early to say this is better, safer or more practical.”

Certain stem cells can be easily grown in the laboratory and can turn into any type of cell in the body, which is called pluripotency. Researchers think these stem cells may one day be used to repair damaged cells and organs in the body, although experiments trying this in people are in very early stages. At first, interest focused on embryonic stem cells, which could be obtained at first only by destroying human embryos.

Several years ago, Shinya Yamanaka of Kyoto University in Japan and other scientists developed a way to turn cells from the body, such as skin or blood cells, into stem cells, avoiding the need to destroy embryos. That work won Yamanaka a Nobel Prize.
But creating those induced cells requires genetic changes to the cells, raising some questions about whether they can be used for medical therapy.

The new technique does away with deliberate genetic changes. Instead, it involves subjecting specialised cells, like blood or skin cells, to stress.

The researchers in Kobe and Boston tried various stresses, including squeezing the cells, but found that bathing the cells for half an hour in a mildly acidic solution seemed to work best. The technique worked for cells taken from various organs of newborn mice, but the efficiency was highest using white blood cells.

The mice from which the cells were taken had been genetically engineered so their cells would glow green if Oct4, a gene associated with pluripotent cells, was active.

After the acid bath, the cells were grown in culture. Many died from the exposure to acid, but among those that survived, many were glowing green by the seventh day. The researchers called these STAP (stimulus-triggered acquisition of pluripotency) cells.

To prove that STAP cells could indeed turn into every cell type in the body, researchers injected the cells into early mice embryos. These embryos grew into mice, called chimeras, with cells derived from the STAP cells in all tissues of their bodies. The mice could reproduce and pass along the genetic characteristics from those cells.

The fact that descendants of the STAP cells could function in mice and their offspring also provided evidence that the cells were not abnormal.

If the technique is to be used to treat patients, it would have to work with cells taken from adult humans, not newborn mice.

Vacanti said that researchers had replicated the work using adult monkey cells and skin cells from newborn human babies, but not yet from human adults.

He said the research stemmed from work years ago by his lab and others that appeared to find pluripotent cells in the bodies of adult people or animals. He said he had begun to suspect that researchers were not actually finding stem cells in the body but rather creating them through the stress from the manipulation of the cells in the laboratory.

It has taken several years of work to demonstrate this. Much of it was done by Haruko Obokata, who started as a graduate student in Vacanti’s lab and is now a biologist at Riken. She is the lead author of the two papers in Nature.

The STAP cells, under the right culture conditions, can form material for the placenta, not just the embryo, which might allow an animal to be cloned just by putting some of its STAP cells into a uterus. Vacanti said that one researcher, whom he declined to name, had tried that with mice but had not succeeded.

Scientists said that it would be interesting to understand how and why stress leads already specialised cells to revert to a more primordial state.

There is some speculation this could be a response that has evolved to help organisms survive trauma. The new study “confirms that cell fate is far more complex than we thought,” said Jeanne F Loring, Director of Center for Regenerative Medicine at the Scripps Research Institute in San Diego. “It appears that at least some cell types are especially sensitive to stimuli that can completely change their character.”

Ding said that since stem cells could form tumours, the findings might help explain why stress appeared to increase the risk of cancer.

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