A LITTLE stress is all it took to make new life from old. Adult cells have been given the potential to turn into any type of body tissue just by tweaking their environment. This simple change alone promises to revolutionise stem cell medicine.
Yet New Scientist has also learned that this technique may have already been used to make a clone. "The implication is that you can very easily, from a drop of blood and simple techniques, create a perfect identical twin," says Charles Vacanti at Harvard Medical School, co-leader of the team involved.
Details were still emerging as New Scientist went to press, but the principles of the new technique were outlined in mice in work published this week. The implications are huge, and have far-reaching applications in regenerative medicine, cancer treatment and human cloning.
In the first few days after conception, an embryo consists of a bundle of cells that are pluripotent, which means they can develop into all cell types in the body. These embryonic stem cells have great potential for replacing tissue that is damaged or diseased but, as their use involves destroying an embryo, they have sparked much controversy.
To avoid this, in 2006 Shinya Yamanaka at Kyoto University, Japan, and colleagues worked out how to reprogram adult human cells into what they called induced pluripotent stem cells (iPSCs). They did this by introducing four genes that are normally found in pluripotent cells, using a harmless virus.
The breakthrough was hailed as a milestone of regenerative medicine – the ability to produce any cell type without destroying a human embryo. It won Yamanaka and his colleague John Gurdon at the University of Cambridge a Nobel prize in 2012. But turning these stem cells into therapies has been slow because there is a risk that the new genes can switch on others that cause cancer.
Now, Vacanti, along with Haruko Obokata at the Riken Center for Developmental Biology in Kobe, Japan, and colleagues have discovered a different way to rewind adult cells – without touching the DNA. The method is striking for its simplicity: all you need to do is place the cells in a stressful situation, such as an acidic environment.
The idea that this might work comes from a phenomenon seen in the plant kingdom, whereby drastic environmental stress can change an ordinary cell into an immature one from which a whole new plant can arise. For example, the presence of a specific hormone has been shown to transform a single adult carrot cell into a new plant. Some adult cells in reptiles and birds are also known to have the ability to do this.
To investigate whether the process could occur in mammals, Obokata and colleagues used mice that were bred to carry a gene that glows green in the presence of Oct-4, a protein that is only found in pluripotent cells. The team took a blood sample from the spleenof these mice when they were one week old, isolated white blood cells called lymphocytes, and exposed them to various strong but fleeting physical and chemical stresses.
One batch of cells was exposed to a "sub-lethal" acidic environment, with a pH of 5.7, for 30 minutes. The team then tried to grow the cells in the lab.
Not much happened at first – some cells died, and the rest still looked like white blood cells. But on day 2, a number of cells began to glow green, meaning they were producing Oct-4. By day 7, two-thirds of the surviving cells showed this pluripotent marker, together with other genetic markers of pluripotency – many of which are also seen in embryonic stem cells. In contrast, iPS cells can take four weeks to reach this stage.
The team call their new cells "stimulus-triggered acquisition of pluripotency", or STAP cells.
To make sure they really were pluripotent, the team injected the STAP cells from the spleen into an early-stage mouse embryo, or blastocyst. These are typically five or six days old with about eight cells already formed inside. The STAP cells seemed to integrate themselves into the structure, and the embryo went on to form the three "germ layers" that eventually give rise to all cell types in the body. The embryos developed into pups that incorporated STAP cells into every tissue in their body. These pups subsequently gave birth to offspring that also contained STAP cells – showing that the cells incorporated themselves into the animal's sperm or eggs, and were inherited.
In a second test, the team injected STAP cells into an adult mouse. They wanted to see if the cells formed a type of embryonic tumour called a teratoma – another gold standard test of pluripotency. They did.
The team wondered whether other adult cells might behave in a similar way. So they tried the acid-bath technique on brain, skin, muscle, fat, bone marrow, lung and liver tissues from one-week-old mice. Although the efficiency varied, the same thing happened in each case. In unpublished results, Vacanti says they have now found the procedure appears to work on cells from much older animals, including some from adult primates. He cautions though that these studies have yet to be completed.
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