How to reset a cell

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Researchers report a surprisingly easy method to change a specialized cell, such as muscle or bone, into becoming a universal stem cell. Stem cells are immature cells that can be coaxed into becoming specialized cells — and they hold a lot of potential for treating sickness and disease

The body needs many different types of stem cells to replace sick, aging or dying cells in its many different tissues. An embryo, a ball of unspecialized cells that will grow into an animal with a backbone, is different. Scientists describe its stem cells as universal “blank slates,” because each can mature into any type of tissue. Now researchers have found a way to create stem cells that mimic the universal role of embryonic cells.

Their method is simple: Just dip the specialized cell briefly in acid. This doesn’t work all of the time. But it did work for 7 to 9 percent of cells taken from newborn mice. And that success rate has surprised a large number of scientists.

Haruko Obokata and her coworkers showed that other ways of stressing a baby mouse’s cells, such as squeezing them, also worked like a reset button. Obokata is a stem-cell biologist at the RIKEN Center for Developmental Biology in Kobe, Japan. She also works at Harvard Medical School in Boston, Mass.

She and her coworkers described the stem-cell making experiments in two papers in the Jan. 30 issue of Nature.

“It’s fascinating. It’s perplexing. It’s potentially profound, but leaves a lot of reasons to scratch my head,” George Daley told Science News. He studies stem cells at Boston Children’s Hospital and Harvard Medical School. The new findings are “begging to be replicated,” he says. Replication is when other scientists perform the same experiment to see if they get the same results. Daley’s team is working on that now.

Other ways exist to turn ordinary cells into stem cells. These methods tend to be much more complicated, however. One requires removing cells from embryos. Another requires removing the nucleus from a specialized cell and inserting it into an egg cell. In yet another method, scientists turn on certain genes to reset cells into stem cells.

Finding an easy way to turn specialized cells into stem cells could provide advances in many areas of medicine. Easy-to-make stem cells could be used to replace cells in diseased organs.

This might one day help people with such brain diseases as Parkinson’s or Alzheimer’s. It might also help replace diseased cells in the pancreas (seen in diabetes) or the liver cells damaged by hepatitis. Because scientists could use the new stem cells to make any tissue in a test tube, they might have an easier time studying certain diseases and treatments. The new stem cells might one day even be useful in overcoming some conditions that prevent a woman from becoming pregnant or from successfully carrying a baby until it’s ready to be born.

Called STAP cells, the new stem cells can change into more types of cells than other lab-made stem cells. The stem cells in an embryo, for example, are pluripotent. That means they can grow into any type of tissue. STAP cells can do this, too, but also make a placenta. This organ nurtures a fetus in the womb. Other stem cells have a hard time growing into a placenta.

In its new study, Obokata’s team bathed blood, skin, brain, muscle, fat, bone marrow, lung and liver cells from newborn mice in an acid solution. The technique also worked on cells from older mice, but not as well. Now, they’ve started testing the method on human cells.

Many biologists have a hard time believing the new findings. Dieter Egli is one. He’s a stem cell researcher at the New York Stem Cell Foundation. He says he can’t imagine how squeezing or acid-dipping a cell resets it.

“If I were to describe this over a coffee break to one of my colleagues,” he told Science News, “they’d say, ‘You must be kidding.’”

Cells in the body undergo stress all the time. So if this is all it takes to reset a cell into a pluripotent form, then it’s hard to imagine how the body keeps its cells in line, Egli says.

However, if the new method does work as well in people as it seems to do in mice, then it offers an exciting new way to create stem cells. More studies will be needed to confirm that the new method also can reliably engineer stem cells as effectively as current techniques. 

Update, February 19, 2014:

There’s now a concern that the findings described above may be too good to be true. That’s why Japan’s RIKEN Center for Developmental Biology, where the lead scientist works, has begun probing whether the new studies might be flawed, according to reports in several news publications.

RIKEN launched its investigation after online commenters reported that images in the two Nature papers may have been improperly altered. In addition, several scientists have had noted that when they tried to repeat the work they didn’t get the same findings.

Stay tuned for more updates.

Update, July 3, 2014:

In the July 3 Nature, authors of the stem-cell papers (reported above) owned up to substantial problems with their January claims. They said that mistakes in their initial work now make these researchers doubt that the phenomenon they had reported is real. As a result, the authors are retracting their papers — pulling them from Nature. (In a sense, it’s now as if the journal had never published them. One difference: The journal will keep the papers on its website, marked as retracted).

It’s an extreme move. A retraction of published research occurs only when reported data is found to be unreliable or unsupportable. Retraction of research can permanently tarnish a scientist’s reputation, especially if the reason for the retraction is fraud or some other serious misconduct.

RIKEN is the research institute in Japan where much of the now-retracted work had been done. It has been probing into the controversy. In April, it reported that the lead scientist (and possibly some others) had plagiarized material — copied passages without saying where the text originally came from. It also found that the scientists had improperly manipulated their data.

As a result, RIKEN concluded that the study’s lead author, Haruko Obokata, is guilty of misconduct. Obokata disputes that charge. But in the retraction notice, she and her co-authors describe five additional errors, including pictures of the same cells or embryos labeled as different cells or embryos.

Meanwhile, since January researchers in other labs have attempted to replicate the initial reported results. To date, none has been successful. RIKEN is giving Obokata five months to conduct experiments to show that her original findings are real. And all of her research will be videotaped. — Tina Saey

Power Words

acid  A chemical that increases the level of hydrogen ions in a solution.

Alzheimer’s disease  An incurable brain disease that can cause confusion, mood changes and problems with memory, language, behavior and problem solving. No cause or cure is known.

cell  The smallest structural and functional unit of an organism. It is typically too small to see with the naked eye.

diabetes  A disease where the body either makes too little of the hormone insulin (known as type 1 disease) or ignores the presence of too much insulin when it is present (known as type 2 diabetes).

embryo  A ball of unspecialized cells that will grow into a vertebrate, an animal with a backbone.

fetus  The term for a mammal during its later-stages of development in the womb. For humans, this term is usually applied after the eighth week of development.

gene  A segment of DNA that codes, or holds instructions, for producing a protein. Offspring inherit genes from their parents. Genes influence how an organism looks and behaves.

nucleus A dense structure present in many cells. Typically a single rounded structure encased within a membrane, the nucleus contains the genetic information.

Parkinson’s disease  A disease of the brain and nervous system that causes tremors and affects movement, memory and mood.

pluripotent  A term that means having many possibilities. In medicine, pluripotent is an adjective used to describe a type of stem cell that can mature into any other type of cell in the body.

stem cell  A “blank slate” cell that can give rise to other types of cells in the body. Stem cells play an important role in tissue regeneration and repair.

tissue  A large collection of related, similar cells that together work as a unit to perform a particular function in living organisms. Different organs of the human body, for instance, often are made from many different types of tissues. And brain tissue will be very different from bone or heart tissue.