At first, then, Yamanaka set about to determine how mouse embryonic cells maintain their pluripotency, the ability to differentiate into any body cell type. He hypothesized that certain proteins would be evident in mouse embryonic cells but not in differentiated cells. He also thought that introducing the genes for these proteins—specifically, transcription factors, which control the activity of other genes—into a normal skin cell’s chromosomes would transform it into an embryonic cell.
After four years of experimentation, he uncovered 24 factors that, when added to ordinary mouse fibroblast cells and subjected to the correct culturing procedures, could create pluripotent cells virtually identical to stem cells. Yamanaka kept examining each factor and found that none could do the job alone; instead a combination of four particular genes did the trick. In 2006 he published a landmark article in Cell identifying them: Oct3/4, Sox2, c-Myc and Klf4.
News of the stunning feat prompted scientists around the world to try to reproduce it using human, rather than mouse, cells. In 2007 Yamanaka reported that triumph with the four transcription factors at the same time as Thomson’s team. “It is actually fairly straightforward to repeat what we have done,” Thomson told the press at the time—still, researchers have likened the breakthrough to turning lead into gold.
The achievement sparked many investigators to switch their efforts from embryonic stem cells to the induced versions. Yamanaka and others have now derived iPS cells from a variety of tissue types, including liver, stomach and brain, and turned the iPS cells into skin, muscle, gut and cartilage, as well as neural cells that can secrete the neurotransmitter dopamine and heart cells that can beat in sync.
Two big safety issues, though, will keep iPS cells out of the clinic for a while. One is that the transcription factor c-Myc happens to be a powerful cancer gene, and the cells produced by Yamanaka’s team tended to become cancerous. “Making iPS cells is very similar to making cancer,” he explains. In principle, c-Myc may not be necessary: in mice, Yamanaka and a group led by Rudolf Jaenisch at the Massachusetts Institute of Technology found a way to avoid using c-Myc, in part, by optimizing culture conditions. Out of 100 mice implanted with iPS cells created without c-Myc in Yamanaka’s lab, none died after 100 days, compared with six out of 100 that died of tumors when c-Myc was used.*
The other risk is the vector used to deliver the genes into target cells—namely, retroviruses. The process results in stem cells full of viruses. Moreover, retroviruses can induce mutations in the cells that lead to cancer. Researchers may soon overcome this hurdle, too. In September a team at the Harvard Stem Cell Institute announced the creation of mouse iPS cells using as a vector the adenovirus, which is safer than retroviruses. In October, Yamanaka’s lab reported success using plasmids, or circular pieces of DNA. Other retrovirus alternatives include proteins and lipid molecules.
Although the surge in interest has led to rapid developments and much competition among labs, Yamanaka and others do not think that iPS cells can replace their embryonic counterparts yet. “We don’t yet know if embryonic stem cells and iPS cells are truly equivalent,” says Konrad Hochedlinger of Massachusetts General Hospital’s Center for Regenerative Medicine. He adds that “at this point, iPS cells are a powerful additional source of pluripotent cells. Time will tell if iPS cells will at some point replace embryonic stem cells. It would be premature to make such a decision now.”
But while insisting iPS cell work remains far from being clinic-ready, Yamanaka trumpets its vast potential for conditions such as diabetes, spinal cord injury, Parkinson’s and even, he chuckles, baldness. “This enormous and striking finding provides a clear framework for regenerative medicine and cell therapy,” says Shinichi Nishikawa, director of the Laboratory for Stem Cell Biology at Japan’s RIKEN Center for Developmental Biology.
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19 Comments
Add CommentThe good doctor is the answer to our prayers...his findings will ultimately remove the need for using human stem cells to treat disease at the expense of human life.
Reply | Report Abuse | Link to this"A Farewell to Embryonic Stem Cells? ...moral debate surrounding embryonic stem cells...." ---- Where does SCIAM get their reporters? From the local mini-mall revivalist church?! ---- Induced pluripotent stem cell research has merits on its own right, but it is certainly not a substitute. You can only say "Farewell" to stem cells only if you want to set back research for at least a generation. --- And, there is "moral" debate about the "personhood" of stem cell and embryos, only in the delusional minds of those, who have an imaginary deity floating in the void of their heads. ---- This is a poorly written and span article, about an otherwise worthy subject.
Reply | Report Abuse | Link to thisThat's great news. Now we can go back to throwing out those embryos with the trash like we did before we found a use for them.
Reply | Report Abuse | Link to thisYay for idiots.
But, what about the rights of induced pluripotent stem cells? If they can be grown into human life, their individual rights need to be protected. Any living cell that contains human DNA absolutely MUST be grown into a human being. After all, there are not enough humans in the world, our life is worth more than every other kind of life on earth. Mangle other animal life all you want, but manipulating microscopic human cells... now you've gone too far. And how dare a woman not fertilize every egg she has?!?! Ugh.
Reply | Report Abuse | Link to thisThis will not stop the calls for embryonic stem cell research, because it isn't about the stem cells. It's about abortion. It's no different than the legalize pot crowd touting the wonders of hemp.
Reply | Report Abuse | Link to thisAh, the wonders of hemp. Truly Jah-sus was on fire the day he created hemp.
Reply | Report Abuse | Link to thisThere is nothing wrong with marijuana. GOD made EVERYTHING for man. To withold it is a sin. Now; I found an interesting article last night on stem cell research and thought I would share it.
Reply | Report Abuse | Link to thisEmbryo ethics
http://www.boston.com/news/globe/ideas/articles/2007/04/08/embryo_ethics/?page=1
Although Bush would ban the use of such embryos in federally funded research, he has not called for legislation to ban the creation and destruction of embryos by fertility clinics.
But if embryos are human beings, to allow fertility clinics to discard them is to countenance, in effect, the widespread creation and destruction of surplus children. Those who believe that a blastocyst is morally equivalent to a baby must believe that the 400,000 excess embryos languishing in freezers in US fertility clinics are like newborns left to die by exposure on a mountainside. But those who view embryos in this way should not only be opposing embryonic stem cell research; they should also be leading a campaign to shut down what they must regard as rampant infanticide in fertility clinics.
Someday, the average Joe-the-Moron will understand the difference between humans and human cells. Then, all this will be pointless debate and we can all ride unicorns into the sunset o'hope.
Reply | Report Abuse | Link to thisTheophys, if I understand you correctly, you are suggesting that an embryo is merely a collection of human cells.
Reply | Report Abuse | Link to thisThis is not the case. An embryo is a unique human being. We don't suddenly become human at some point during gestation. It happens at conception.
Anyhoo, I'm all for innovative methods of stem cell research, just not with embryos.
That's your religious opinion. I mop up cells and throw them in the toliet, gonna charge me with murder?
Reply | Report Abuse | Link to thisAt that point it is only a 'potential ' human being. Not so far up the ladder than an egg and a sperm. Huh.
Reply | Report Abuse | Link to thisI like that pix of him. It's like; Hahahaha....I got'cha! I know something you don't know.....
Reply | Report Abuse | Link to this"After all, there are not enough humans in the world, our life is worth more than every other kind of life on earth...And how dare a woman not fertilize every egg she has?!?! Ugh."
Reply | Report Abuse | Link to thisWe all started the same, and the way different organisms have evolved does NOT mean that one is more important than the other. (That's what Nazis based things on, after all.) As for fertilizing ever egg--do you even realize how many eggs we have? Menstruation as we know it would be obliterated if we gave birth to every baby possible. Have each of your sperm create a new child, and then we'll talk.
"GOD made EVERYTHING for man. To with[h]old it is a sin."
The mere existence of "God" is debatable. Let's not hold this guy up to creating everything. It's a big responsibility.
I think you're both full of crap. This is science, not church, people.
For some people it's both. Do you mind that?
Reply | Report Abuse | Link to thisThose of you who think the human embryo isn't a human being except according to religious belief, do yourselves a favor and open a biology textbook. As I work in education, I go through several. Biology textbooks correctly state fertilization as the beginning of a new individual's life. I find it rather disconcerting that so many people confuse cells with actual embryonic human beings.
Reply | Report Abuse | Link to thisMany scientists are deciding to move away from embryonic research and towards the less problematic substitutes, for reasons of both ethics and practicality. Take a note from them.
Funny, when someone in a scientific community states their view that doesn't agree with another's view, the ones who hold an atheistic view consistantly resort to personal attacks, even before anything is said about religion. A want-to-be scientist should realize that not everyone against embryonic stem cell research is so because of any religiuos belief.
Reply | Report Abuse | Link to thisFully agree with EvolvingApe. Induced pleuripotent cells are NOT the same as stemcells. IPS cells may never be used in stemcell therapy because of the dangers posed by the transcription agents and the retrovirus vectors. In order to repair, lets say, damaged myocardial tissue in-vivo, you need a safer alternative - embryonic stemcells.
Reply | Report Abuse | Link to thisUnfortunately, the god-morons keep on hampering this reseach with their archaic moral arguments developed for a band of aggressive nomads lost in the desert 2000+ years ago.
To xHelena.. how did you not get that the first comment is completely sarcastic?
Reply | Report Abuse | Link to this"After all, there are not enough humans in the world, our life is worth more than every other kind of life on earth...And how dare a woman not fertilize every egg she has?!?! Ugh."
Dripping with sarcasm...
When life actually begins is still a mystery in science. Does it start with the fusion of the pronuclei? or is it at the calcium wave?
Reply | Report Abuse | Link to thisFor me it is when the heart begins to beat as otherwise this ball of cells wouldnt survive without our help.
And yes Im a biologist who believes in God... Who says the two cant mix...