05 Mar 2014 01:22

STAP discovery could prove more important than iPS cells

Haruko Obokata, a researcher at the Riken Center for Developmental Biology in Kobe, points to stimulus-triggered acquisition of pluripotency (STAP) cells on a screen on Jan. 28. (Mainichi)
Haruko Obokata, a researcher at the Riken Center for Developmental Biology in Kobe, points to stimulus-triggered acquisition of pluripotency (STAP) cells on a screen on Jan. 28. (Mainichi)

The newly discovered technique of producing pluripotent cells just by immersing somatic cells in mild acidic solution has sent shockwaves through the scientific community, with one expert describing the magnitude of the finding as greater than that for induced pluripotent stem (iPS) cells.

A team of researchers at Riken and other institutions made the discovery of stimulus-triggered acquisition of pluripotency (STAP) cells, which could rewrite the future of regenerative medicine by overcoming medical challenges posed by iPS and embryonic stem (ES) cells.

Behind the scientific breakthrough lie five years of trial and error and warm support from experienced Japanese researchers for the team.

"Acquiring pluripotency by simply giving stress to cells comes as a shock greater than that for iPS cells," said Hiromitsu Nakauchi, professor at the University of Tokyo who is working on blood regeneration using iPS cells.

Arata Honda, associate professor at the University of Miyazaki who has been engaged in research on iPS cells, commented, "It is such a tremendous achievement, which goes beyond a surprise and is astounding."

Because the latest finding is based on mice experiments, experts say whether the technique can be applied to human body cells holds the key to the development of the research. The mechanism of cell reprogramming and the reason why it is highly effective to immerse cells in mild acidic solution in employing the technique are yet to be revealed.

Takashi Tada, associate professor at Kyoto University, said, "If this can be applied to human beings, the finding could lead to 'post-iPS' cells that can pave the way for applications in medicine."

So far, STAP cells are known to be capable of transforming themselves into placental cells -- a stunt that iPS and ES cells are unable to perform -- and are closer to fertile eggs in terms of pluripotency, making it easier to produce cells for specific purposes.

Because iPS cells are generated by gene introduction, they pose the risk of turning cells carcinogenic from chromosomal damage. STAP cells, meanwhile, were found to be free of chromosomal damage and didn't turn carcinogenic when transplanted into mice, suggesting that STAP cells boast greater safety than iPS cells. Although STAP cells are not capable of multiplying themselves indefinitely like iPS and ES cells do, the research team succeeded in producing stem cells with the ability to proliferate by changing culture conditions.

Yoshiki Sasai, deputy head at the Riken Center for Developmental Biology, said, "The finding that somatic cells in animals have the function of reprogramming themselves spontaneously overturns common knowledge in biology."

The method of immersing cells in mild acidic solution for just 30 minutes is so easy that, "Even students might be able to produce STAP cells in their lab experiments," said Honda. The fact that such a production method doesn't require special materials or techniques may also accelerate the research.

"The world will hereafter witness severe competition (involving STAP cell research) equivalent to that for iPS cells," said Atsuo Ogura, a senior Riken official.

"At first no one believed in me. I thought about quitting time and again, crying countless nights," said Haruko Obokata, 30, a unit leader at the Riken Center for Developmental Biology who led the research team, during a press conference on Jan. 28.

She started contributing her research papers to leading scientific journals around 2009, but her surprising research results continued to be turned down, with comments like "It's inconceivable." Even the acclaimed British scientific journal "Nature," which recently published her paper, had once rejected her contribution in April 2012, with a referee commenting that she was deriding the history of cell biology.

It was in 2008 when she was studying under professor Charles Vacanti at Harvard University that she finally saw light at the end of the tunnel. Vacanti believed at the time that bodies inherently possess pluripotent stem cells that can turn into various tissues and organs. Under his guidance, Obokata conducted experiments in which clumps of various types of mice cells were put through ultrafine glass tubes.

It eventually turned out that the more the cells were stimulated, the more the number of pluripotent stem cells formed. "It may be that pluripotent stem cells are newly produced by stimulating them from the outside," Obokata surmised. The experiments went on, this time submitting cells to harsher environments such as not supplying nutrients to the cells and placing them under high temperatures. The most effective method, it emerged, was to immerse somatic cells in mild acidic solution. Vacanti praised Obokata as a "rising star" during an interview with the Mainichi Shimbun.

Subsequently, leading Japanese researchers helped out the research team in demonstrating the potency of STAP cells. Teruhiko Wakayama, professor at the University of Yamanashi who is known for creating the world's first cloned mouse, joined an experiment in which STAP cells were injected into a fertilized egg to produce a mouse with STAP cell-origin cells all over its body. The experiment proved a success, with a "chimera mouse" born exactly the way they had expected and demonstrating the capacity of STAP cells. "Something implausible has happened, I thought," Wakayama recalls the moment the experiment was determined a success.

The research team contributed its paper to Nature once again a year later after collecting more convincing experimental data and complying with the journal's request of additional experiments.

"I owe so much to professionals in stem cell research, who kindly provided me with advice," Obokata said.

January 30, 2014(Mainichi Japan)