A team of Boston and Japanese researchers stunned the scientific world Wednesday by revealing a remarkably simple and unexpected way to create stem cells able to give rise to any tissue in the body.
To transform mature cells into powerful stem cells that are a biological blank slate, the team simply bathed them in an acid bath for half an hour. The technique appears to be far easier and faster than current methods for creating these cells, which scientists are racing to develop into therapies for a range of diseases.
The result is “shocking,” “astounding,” “revolutionary,” and “weird,” said scientists not accustomed to using such exuberant words to describe new research findings. 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, although further study and confirmation of that preliminary result is needed.
“It’s just a wonderful result; it’s almost like alchemy,” said Douglas Melton, co-director of the Harvard Stem Cell Institute, who was not involved in the research 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.”
The discovery less than a decade ago that it was possible to “reprogram” mature human cells to become stem cells was hailed as a breakthrough and was recognized with a share of the Nobel prize in 2012. It spawned a huge push, funded with hundreds of millions of dollars in public and private money, to devise ways to use the cells to treat diseases in which tissues are injured or lost, such as juvenile diabetes or heart failure.
The new work reveals a potentially cheap, fast, and simple avenue to create the powerful cells—by exposing mature cells to environmental stress instead of having to manipulate the genes inside the cell’s nucleus. If the finding is replicated by other scientists, it also promises to yield fresh 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 and began working with a team including his younger brother Martin, a pathologist, to find one.
In a 2001 study, they reported the discovery of a new kind of stem cell that they isolated with a technique that had been used to isolate neural stem cells: they mashed up mature tissue and passed it through ever-smaller pipettes to sift out a new type of cell they called 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 the 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 genes are active. Further work showed that other types of stress, such as growing the cells in low oxygen or bathing them in a solution that is more acidic than milk but less than juice, transformed a portion of the cells into STAP cells—short for stimulus-triggered acquisition of pluripotency.
STAP cells had genetic markers that were signatures of stem cells, but they weren’t quite the same as true stem cells found in embryos. They didn’t live as long, and they couldn’t multiply indefinitely. But the researchers found 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 became 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 who 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 induced pluripotent stems cells—which are reprogrammed by adding genes or chemicals and known as iPS cells. This is now the way that most scientists produce pluripotent cells with 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,” Nobel laureate Shinya Yamanaka, who shared the Nobel for discovering the cellular reprogramming method for creating iPS cells, wrote in an e-mail.
Vacanti believes that it’s possible what the researchers uncovered is part of the body’s natural healing mechanism—that the more stringent the stress on the cell, the further they get kicked back to a pluripotent state.
Other researchers, while praising the work, expressed doubt about Vacanti’s hypothesis. While emphasizing that it appears to be a powerful and impressive result, they said they aren’t sure the process would naturally occur in living mammals.
Dr. George Q. Daley, director of the stem cell transplantation program at Boston Children’s Hospital, said that it had been a long time since he read a scientific paper and felt both so amazed and perplexed. The technique must be repeated in many labs, he said, and probed to see whether it could be useful, but it’s a provocative reminder of the malleability of cells—a concept that has undergone a revolution in biology over the past decade.
“It’s a startling result that makes you stand up and go, ‘Wow!’” Daley said. “With an equal dose of amazement and skepticism.”