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Scientists discover a new, simpler way to make stem cells

In preliminary research, Brigham and Women’s scientists believe they have reprogrammed human cells to become stem cells, seen here through the microscope.

Yoon S. Byun/Globe Staff

In preliminary research, Brigham and Women’s scientists believe they have reprogrammed human cells to become stem cells, seen here through the microscope.

Editor’s note: The studies described in this article were retracted from the journal Nature by the authors in July 2014, due to problems with images of cells and amid allegations of fraud.

A team of Boston and Japanese researchers stunned the scientific world Wednesday by revealing a remarkably simple and unexpected way to create stem cells that can become any of the diverse cell types in the body.

The secret? Just bathe mature cells in acid for half an hour. The result is “shocking,” “astounding,” “revolutionary,” and “weird,” said scientists not accustomed to using such exuberant words to describe research findings.

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The technique appears to be far easier and faster than current methods for creating stem cells, which scientists are racing to develop into therapies for a range of diseases, such as juvenile diabetes and heart failure.

The finding has been officially reported only in mice, but human studies are underway. Researchers at Brigham and Women’s Hospital said that over the weekend they made what appears to be a human version of the stem cells using the same technique, although this preliminary conclusion needs to be confirmed.

“It’s just a wonderful result; it’s almost like alchemy,” Douglas Melton, who is codirector of the Harvard Stem Cell Institute and was not involved in the research, said of the two mouse studies published Wednesday in the journal Nature. “It says one has found a way to reveal the hidden potential of cells with a relatively straightforward method.”

Yoon S. Byun/Globe Staff

Charles Vacanti (right), with Koji Kojima, has been at the vanguard of stem cell creation.

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Before 2006, embryonic stem cell research was conducted with cells from destroyed embryos, sparking protest on ethical and religious grounds. The discovery that embryonic-like stem cells could be produced in a laboratory by “reprogramming” mature cells was welcomed as a way to potentially avoid that controversy.

It was also hailed as a research breakthrough and was recognized with a share of the Nobel Prize in 2012. The discovery escalated a push, funded with hundreds of millions in public and private dollars, to devise ways to use the cells to treat diseases in which tissues are injured or lost.

The new work reveals a potentially cheap, fast, and simple avenue to create the powerful cells — by exposing mature cells to environmental stress, in this case the acid bath — instead of having to manipulate the genes inside the cell’s nucleus, the main method now used.

If the finding is replicated by other scientists, it also promises to yield insights into the behavior of cells and demonstrates that important scientific advances often emerge from unexpected areas of inquiry.

The approach is so simple and so out-of-the-box that it might never have been tried if it hadn’t been for the persistence and curiosity of Dr. Charles Vacanti, a Brigham and Women’s anesthesiologist working largely outside the field of stem cell science.

Vacanti is best known for his work on the “earmouse,” the flashy tissue engineering feat of growing a human ear on the back of a mouse that made headlines in 1995. Vacanti wanted to find a better cell type to use on tissue engineering projects.

In a 2001 study, he and colleagues reported the discovery of a new kind of small stem cell that seemed able to survive very harsh conditions. They called the new type of cell a “spore-like cell.”

“Our lab was pretty ridiculed,” Vacanti recalled, of the scientific response. After that, “I kind of kept it to myself.”

Then, six years ago, a Japanese graduate student named Haruko Obokata arrived in Vacanti’s laboratory. Vacanti asked if she would take up the work again — doing it more rigorously and addressing the valid questions critics had raised.

In the intervening years, his ideas about the research had also shifted. What if, instead of isolating existing stem cells from the tissue, he had actually been creating them through a harsh extraction procedure? Were the cells reverting to stem cells because of the stresses of the procedure, or were they already there? Obokata began the work.

Ultimately, the team found that the environmental stress was producing the stem cells. The mechanism is not fully understood, but scientists saw telling changes in the pattern of molecules that attach to DNA and determine which of a cell’s genes are active.

Further work showed that other types of stress, such as squeezing cells through tiny tubes and bathing them in a solution more acidic than milk but less so than juice, transformed a portion of newborn mouse blood cells intoa kind of stem cell the scientists named STAP cells. These cells were shown to be similar in some ways to stem cells from embryos but didn’t live as long, and couldn’t multiply indefinitely.

The researchers found, however, that if they put the STAP cells in lab dishes with the right growth medium — a nutrient gel that is used to help embryonic stem cells multiply — the STAP stem cells behaved just like embryonic stem cells.

“It’s good quality. They did the right experiments,” said Rudolf Jaenisch, a stem cell biologist at the Whitehead Institute, an MIT-affiliated research laboratory. Jaenisch said that his lab would likely try to repeat the work. “We need to learn much more about these cells.”

Obokata, now a scientist at the RIKEN Center for Developmental Biology in Japan, said during a press conference that it was still unclear what the therapeutic use of these cells would be, or how they would compare if put side-by-side with embryonic stem cells, or with so-called iPS cells, created by adding genes or chemicals to mature cells. This is now the way that most scientists produce pluripotent cells, which have the ability to develop into any tissue in the body.

“From a practical point of view toward clinical applications, I see this as a new approach to generate iPS-like cells,” Shinya Yamanaka, who shared the Nobel for discovering the cellular reprogramming method for creating iPS cells, wrote in an e-mail.

Although the new technique avoids the kind of debates that swirled around embryonic stem cell research, it may raise future ethical concerns. The Rev. Tadeusz Pacholczyk, director of education at the National Catholic Bioethics Center, wrote in an e-mail that the study suggests the cells appear to be even more versatile than embryonic stem cells, able to give rise to tissues such as placenta.

“While the derived cells do not appear to be organisms/embryos themselves, one can envision future scenarios, as research progresses, in which regular body cells could be coaxed into becoming” cells capable of developing into an adult organism, Pacholczyk wrote.

Dr. George Q. Daley, director of the stem cell transplantation program at Boston Children’s Hospital, said it has been a long time since he has read a scientific paper and felt both so amazed and perplexed. The technique must be repeated in many labs, he said, and studied to see whether it could be useful, but it’s a provocative reminder of the malleability of cells, a concept that has revolutionized biology.

“It’s a startling result that makes you stand up and go, ‘Wow!’ ” Daley said, “with an equal dose of amazement and skepticism.”

Carolyn Y. Johnson can be reached at cjohnson@globe. com. Follow her on Twitter @carolynyjohnson.
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