STEM CELL UPDATE: It was hoped that iPS cells could get around some ethical concerns regarding the use of embryonic stem cells, but new research suggests iPS cells are not a good substitute
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The act of reprogramming cells to make them as capable as ones from embryos apparently can result in aberrant cells that age and die abnormally, suggesting there is a long way to go to prove such cells are really like embryonic stem cells and can find use in therapies.
Embryonic stem cells are pluripotent, able to create all cell types, save more embryonic tissue. To avoid the controversy surrounding these cells, scientists around the world have explored reprogramming mature cells to make them just as potent, with the hope being that such induced pluripotent stem (iPS) cells might one day help replace diseased or damaged tissue. Rapid progress is being made toward controlled differentiation of human iPS cells into specific tissue types, such as heart, neuron, liver, pancreas and eye.
"You hear all this dialogue in the media and scientific community about how iPS cells are just the same as embryonic stem cells, how they can solve the whole controversy by removing the need for embryos," says stem cell scientist Robert Lanza, chief scientific officer at Advanced Cell Technology in Worcester, Mass. "There's a lot of excitement about iPS cells, but no one wants to hear about the problems."
Lanza and his colleagues investigated a range of cell types derived from eight human iPS cell lines and 25 embryonic stem cell lines. At first they found that human iPS cells could indeed generate blood vessel, blood precursor and retinal cells with characteristics similar to ones derived from embryonic stem cells, albeit with significantly reduced efficiency.
Further study, however, revealed cells derived from iPS cells had significantly higher rates of cell death, or apoptosis, than ones from embryonic stem cells. Moreover, whereas the blood vessel cells that resulted could also form capillarylike structures, they and the retinal cells aged prematurely, losing their ability to divide.
In addition, where cells derived from embryonic stem cells are great at proliferating—a potentially critical feature if one wants to grow sufficient numbers of cells for clinical use—ones from the iPS lines were much feebler. "It's not just a little difference, but up to 1,000- to 5,000-fold less activity, the difference between not having enough to coat the tip of a pen to enough to fill a whole test tube," Lanza says.
"We were devastated to find this out," Lanza adds. He notes his company had planned this year to apply to the U.S. Food and Drug Administration to use red blood cells and platelets derived from iPS cells in clinical trials, but "at this point, therapies with these cells are years off."
There were already concerns surrounding the use of iPS cells in therapies because prior studies suggested they were prone to forming cancers. "What our findings show is that the problems with iPS cells don't just involve one or two or a few abnormal iPS cells escaping into the body and forming tumors, but that the whole population of cells is screwed up," Lanza says.
Although no clinical trials involving therapies derived from iPS cells are on the books, researchers are currently testing drugs on them. "Our results are saying that if cells in these experiments are senescing and undergoing apoptosis, any conclusions we draw from that might not apply to what drugs are being tested on them, but from how the cells were derived," Lanza says.
The abnormalities seen with the iPS cells may be related to viruses used to create them. Unpublished results from the researchers hint that significantly fewer anomalies are seen in iPS cells created via virus-free reprogramming strategies, such as ones that use proteins or small-molecule drugs. "The most obvious explanation there is that one cannot slice up DNA with viruses and not expect consequences," Lanza says. He and his colleagues detailed their findings online February 11 in the journal Stem Cells.
"This shows iPS cells have a lot of problems, but that doesn't mean they don't have potential—just not with the established methodologies used to create them," says tissue engineer Anthony Atala, director of Wake Forest University Baptist Medical Center's Institute for Regenerative Medicine in Winston–Salem, N.C. "It's a solvable problem, but it looks as if one should look away from methods that don't genetically modify the cell."
Future research should not only compare how embryonic stem cells, iPS cells and adult stem cells differentiate, but focus on what effects the niche in which these cells will reside, when transplanted, will have on their characteristics, including tendencies to mutate into cancer cells, notes cell and stem cell biologist Olga Genbacev at the University of California, San Francisco, (U.C.S.F.) School of Medicine. "The major obstacle for this research is time: We need time and coordinated international efforts," she says.
"Rather than being gloom and doom with these results, we should think of them pointing us toward things that are going to have to be fixed," commented developmental and stem cell biologist Susan Fisher at U.C.S.F. "For instance, these undergo senescence early. Well, there are major pathways known to control senescence. We'll want to look at those pathways to understand what's going on in these iPS cells and see if we can repair them."
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16 Comments
Add Commentfrgough, you are either misinformed or are being intentionally deceiving. Embryonic stem cell research does not involve fetuses because embryonic stem cell research does not involve pregnancy. Spin it how you like, but facts are facts.
Reply | Report Abuse | Link to thisIn addition, embryonic stem cells are effective in their own right. If you have been following stem cell research, which by your conservative and misinformed response it appears as if you are not, embryonic stem cell research has made headway. Just last week Stanford managed to create neurons that can have an application to disease therapy. Adult stem cells have limitations and as a result, are limited in their effectiveness in modern therapies. Just b/c this article shows a limitation of iPS, which Yamanaka alluded to in the past, it will soon be remedied through effective and innovative methods. Don't forget stem cell biology is a young field. It is less than a decade old in terms of its boom in 2001-2002, before it was severely slowed down by the former governmental administration. You are very misinformed about embryonic stem cell acquisition, considering that if the stem cells do come from fetuses, the donor consents to donating it from science. Millions of embryos are recycled daily, but why just throw it away if we can extract the stem cells and study them so that maybe one day, a life could be saved. This conservative Republican view is highly flawed and is due to misinformation. Before deriding the field, do some research about the stringent guidelines and consistent FDA and government regulation that goes on to ensure the sanctity of all scientific studies involving stem cells.
Reply | Report Abuse | Link to thisIn addition, embryonic stem cells are effective in their own right. If you have been following stem cell research, which by your conservative and misinformed response it appears as if you are not, embryonic stem cell research has made headway. Just last week Stanford managed to create neurons that can have an application to disease therapy. Adult stem cells have limitations and as a result, are limited in their effectiveness in modern therapies. Just b/c this article shows a limitation of iPS, which Yamanaka alluded to in the past, it will soon be remedied through effective and innovative methods. Don't forget stem cell biology is a young field. It is less than a decade old in terms of its boom in 2001-2002, before it was severely slowed down by the former governmental administration. You are very misinformed about embryonic stem cell acquisition, considering that if the stem cells do come from fetuses, the donor consents to donating it from science. Millions of embryos are recycled daily, but why just throw it away if we can extract the stem cells and study them so that maybe one day, a life could be saved. This conservative Republican view is highly flawed and is due to misinformation. Before deriding the field, do some research about the stringent guidelines and consistent FDA and government regulation that goes on to ensure the sanctity of all scientific studies involving stem cells.
Reply | Report Abuse | Link to thisLet us not give up on this technology! This article sounds like it has a bit of a negative bias (ghost-written my a pharma company?) I jest, but seriously, when this science is refined it will provide great new therapies, and end the complaints of those who would classify an embryo as a living organism.
Reply | Report Abuse | Link to thisI believe Robert Lanza is not reliable at all. He has a lot conflict of interest in every paper he produces. He is comitted to give benefits to his company, and iPS cells, which are easy to generate, are a big problem for him. Moreover, if iPS cells are prone to senescence, they must necessarily be less prone to cancer, and not the opposite. Anyway, if he uses old methods to generate iPS cells, as it is the use of viruses, it is not strange the resulting iPS cells are altered.
Reply | Report Abuse | Link to thisIt is obvious that there is no way in the forseable future that the FDA would allow iPS derived cells to be put into humans.
Reply | Report Abuse | Link to thisThe layers of dangers are numerous and probably unsolvable.
The Elephant in the room is the hESC's which have already been approved for clinical trial (Geron)
Research energy and resources should no longer be wasted on iPS cells and should be used on hESC's
Thank you manuel, that is very true, and a point that I overlooked: If iPS cells are subject to "...significantly higher rates of cell death, or apoptosis..." then tumours, for which immortality and unchecked reproduction are family traits, should be less frequent with iPS. These characteristics are mutually exclusive.
Reply | Report Abuse | Link to thiscan anyone find this paper on this?
Reply | Report Abuse | Link to thisRobert Lanza is if not the best,one of the premier scientists in the stem cell field.If he said it,you can take it to the bank.Lanza has already devised a technique to create ESC's without harm to the embryo.ACTC has applied for a trial using such a stem cell line for blindness and will most likely beat Geron and be the first successful ESC treatment.The press and the church continue to repeat the same old stories.Lanza has made the whole embryo death argument a moot point.
Reply | Report Abuse | Link to thisIt's time to let knowledge flourish and let us begin to see the results of this research.Cures instead of management of chronic disease.
Let Lanza sing!
Robert Lanza is one of the premier stem cell scientists in the world.If he said it,you can take it to the bank.Advanced Cell has developed a technique to create ESC's without harm to the embryo.They have already applied for a trial using a stem cell line created this way.They will most probably beat Geron to the proverbial cheese.
Reply | Report Abuse | Link to thisMany in the press as well as the church continue to repeat the same mantra about embryo death.These are the same people who deny global warming and call Obama a socialist.ACTC has made the embryo death argument a moot point.Jt's time to let this amazing research come to fruition and start to cure instead of just managing chronic disease
Let Lanza sing!
Pregnancy or not, we know from basic human reproductive biology that a new human being's life commences at the moment of fertilization, and so there is no difference between destroying an embryonic human being for medical research and killing a born human being for the same purposes.
Reply | Report Abuse | Link to thisDr. Yamanaka and Dr. James Thomson (who first isolated embryonic stem cells in humans) have been quoted with respect to their ethical qualms related to ESCR, and this is just one reason most of the work on ESCR is switching over to work on the more easily managed adult stem cells.
Pregnancy or not, we know from basic human reproductive biology that a new human being's life commences at the moment of fertilization, and so there is no difference between destroying an embryonic human being for medical research and killing a born human being for the same purposes.
Reply | Report Abuse | Link to thisDr. Yamanaka and Dr. James Thomson (who first isolated embryonic stem cells in humans) have been quoted with respect to their ethical qualms related to ESCR, and this is just one reason most of the work on ESCR is switching over to work on the more easily managed adult stem cells.
Rx: "The Elephant in the room is the hESC's which have already been approved for clinical trial (Geron)."
Reply | Report Abuse | Link to thisYeah, yeah, yeah...Geron's been "months away" from clinical trials for about four years now. They'll put out a press release stating that they're about to hold clinical trials, their stock price will shoot up, and then the inherent problems with embryonic research will rear their heads yet again, and Geron will backtrack -- until the next press release, anyway.
And what you conveniently neglected to mention, Rx, is that ADULT stem cells are wiping the floor with embryonic stem cells, and are already being used in clinical trials -- ALREADY helping human beings, INCLUDING paralysis patients.
Time for a retraction! Your headline is completely wrong. This article is about INDUCED PLLURIPOTENT stem cells, not ADULT STEM CELLS. ADULT STEM CELLS are completely different and dont have the problems of EMBRYONIC STEM CELLS or INDUCED PLURIPOTENT STEM CELLS.
Reply | Report Abuse | Link to thisTime to read STEM CELLS FOR NEWBIES!
http://repairstemcell.wordpress.com/stem-cells-for-newbies/
So&
The Trouble With Adult Stem Cellsand Why They Wont Displace Embryonic Ones
should read&
The Trouble With INDUCED PLURIPOTENT Stem Cellsand Why They Wont Displace Embryonic Ones
http://repairstemcell.wordpress.com/2010/02/11/why-induced-pluripotent-adult-cells-wont-end-the-stem-cell-wars-newsweek-com/
Have anyone seen any research that has reliable data proving the impact of the media upon the people's acceptance towards stem cells?
Reply | Report Abuse | Link to thisI don't think any of you follow Scientific American to any degree because on the cover of the May issue they tout iPSC's as if they were the greatest thing to come along for the research yet this artical for Scientific American speaks to it never receiving funding. I find this same contradiction with other mags; Popular Mech, and Popular Sci. say one thing in the news stand copy then do a 180 online.
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