Scientists Can Grow Stem Cells In a Petri Dish 83
rift321 writes "Scientists safely created induced pluripotent stem cells from human stem cells, and grew them in a petri dish. The previous methods for creating iPSC's involved the use of retroviruses, which rendered the stem cells unacceptable for human implantation due to an increased risk of cancer and mutations. The researchers used a safer, albeit slower process to modify the skin cells, using a cell-penetrating peptide to deliver the needed genes into the cell (PDF). I'd like to hear if anyone has some insight into exactly how close that brings us to everyday-use of stem cells for regenerative therapy, and exactly what obstacles remain before such therapies can be put to use."
Wow... (Score:1, Interesting)
Re:Wow... (Score:5, Informative)
One potential problem is that they're using c-myc, an oncogene. [wikipedia.org]
From the actual paper
Tumor cells are often found to have more c-myc protein than they should, and mice which have too much c-myc develop cancer much more frequently. By getting protein in rather than genes expressing the protein into cells, this is probably safer, as the cells aren't going to continue making c-myc presumably, but it is something that needs to be rigorously tested.
I think the chances of it being anything really dangerous are pretty low. You're going to be turning individual cells with this, growing a whole bunch, and differentiating the cells before putting it into a patient. The protein only needs to work on that first cell, and proteins are turned over pretty quickly, it's likely that by the time you got to making new tissues it would already be gone, and any left over would probably be very dilluted to where it won't have an effect.
Also, you can make these cells without it. C-myc was one of the initial four genes used to make plurpotent cells, but a short while later it was shown that c-myc only increases the efficiency. This current method is low-efficiency, and you'd expect the efficiency to drop even lower without c-myc. As the summary points out, they're already working on ways to increase the efficiency, dollars to doughnuts they're going to be trying it without c-myc in the near future.
As far as the question in the summary
I'd like to hear if anyone has some insight into exactly how close that brings us to everyday-use of stem cells for regenerative therapy, and exactly what obstacles remain before such therapies can be put to use."
It puts it a lot closer. Transgenic tissues are much more worrisome than protein-treated tissues. When you give the cell new instructions for how to make proteins that can cause cancer, that's dangerous. Supplying those proteins yourself, not as much.
There is still one major obstacle that's probably a bigger concern: we can deprogram these cells, but you want to be absolutely sure though they're reprogrammed before you put them into a patient. If you want to put new neurons into someone, you have to be sure you've turned all the iPSC into neurons. If you put undifferentiated cells into someone's brain, they tend to develop teratomas, which I think is one of the worst types of tumors to have. They're making strides on that, but I don't think they're to the point where they can say for sure that's not going to happen.
This current breakthrough is absolutely a great thing though, don't mean to diminish it, just that there are other steps.
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At the same time, other scientists have discovered how to stop stem cells from becoming cancerous.
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I would have to disagree with a Teratoma being the worst type of tumor to have (albiet in ones brain of course it could present some serious issues) considering they are mostly benign and very treatable. And on the cool factor you can find some rather interesting things inside of them. I should also say gross factor, as most people do not share my ideas of what is 'cool'
I would wonder how long it would be until
Re:Wow... (Score:4, Informative)
I would have to disagree with a Teratoma being the worst type of tumor to have (albiet in ones brain of course it could present some serious issues) considering they are mostly benign and very treatable. And on the cool factor you can find some rather interesting things inside of them. I should also say gross factor, as most people do not share my ideas of what is 'cool'
You're talking about the teeth and hair? Yeah, that's gross and cool in my book.
I would wonder how long it would be until we can be absolutely sure that we have successfully reprogrammed these cells. I'm not sure that is possible at this point, though someone feel free to correct me on that, as I am not sure of the process.
Yes, it seems like it's the same as stem cell differentiation after the deprogramming, and we've been working on that for some time. You can definitely get stem cells and IPSC to differentiate in culture prior to implanting. For instance the yamanaka paper or the other initial paper detailing iPSC showed you could direct differentiation into cardiac like cells which would beat in the dish. And they had other ways of showing they directed differentiation of some tissues.
However, making a pure culture is an issue for at least neurons. Not really a good way (as of the last review paper on neurogenesis I read, a year old so I could easily be out of date) to make sure you've gotten all the cells to become postmitotic neurons. I know you can get cultures that are enriched with neurons and are at least mostly neurons, but AFAIK implanting that into a spinal cord lesion might get you teratomas there because of a few cells we can't isolate out yet. And there are probably issues with organization of neurons after that as well.
I realize that I'm thinking only of neurons, since I work on neurogensis (sorta). I should have said that I don't think we're there for brain and spinal cord, but don't know about other tissues. Maybe we've figured out how to turn stem cells into all liver cells already. Maybe pancreatic cells, I think I remember hearing something about that. Anyway, I'd amend my statement to "we might be ready for clinical trials with some non-neural tissues with this finding."
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miRNA-145 sounds like it represses transcription of the 3. The current study isn't using transcription of those proteins, the proteins are directly applied to the cells.
Additionally, making sure all cells from an iPSC culture are expressing miRNA-145 before you implant them doesn't strike me as being easy. You could maybe set up some type of screen, to where only cells that express miRNA-145 would live, but then you're again dealing with transgenic tissues, which is generally frowned upon when talking abo
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Finally (Score:1, Funny)
Re:Finally (Score:5, Insightful)
I can manifest those mutant powers I've always wanted!
I'd be happy just to replace my missing teeth !
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You may want to think twice about that. http://www.cracked.com/video_17328_why-having-wolverines-claws-would-suck.html [cracked.com]
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Mass production possible soon? (Score:1)
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Re:Mass production possible soon? (Score:4, Insightful)
This is a new field of technology, sure it needs several breakthroughs and refinements before it becomes practical.
I prefer hearing news about it than no news at all.
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They who? This is, as the authors clearly state, a proof-of-concept method which takes longer and has lower efficiency than previous methods but is hopefully safer. The only people making premature announcements of a miraculous breakthrough or crying wolf etc. are news media, but that is to be expected. What needs to be done now is to improve on this method by using purified proteins, as opposed to HEK293 cell extracts, and making other optimizations. Regarding the applicability of induced pluripotent SCs (
Obstacles?? OBSTACLES??? (Score:1)
There's only one real obstacle. Make it affordable.
Re:Obstacles?? OBSTACLES??? (Score:5, Informative)
And just what do you think you're going to do with it? TFA is a stupid, hype filled mess (as usual). The original article is here [cell.com]. The big deal is thus:
- Pluripotent stem cells MAY (big time maybe) be useful in a wide array of clinical applications.
- Embryonic stems cells are hard to obtain, have ethical issues to some folks.
- Fibroblasts (skin cells) are easy to obtain, not so ethically high strung and easy to grow.
- We've known for a couple of years that you can create what look to be stem cells by infecting fibroblasts using four (count'em only four) separate proteins. That's pretty amazing - the whole differentiation cascade is apparently controlled by a small number of discrete molecules.
- The problem is that to get those proteins inside the fibroblasts you have to use a (real) virus, which is interesting called a "Trojan" since it's "bringing in" foreigners. That is conceptually unappealing because the "stem cells" now have some viral garbage which may or may not interfere with experiments.
- The current research gets said proteins inside the cell using another clever "hack" - a small peptide (apparently derived from HIV infected cells) that allows the bigger proteins to sneak inside and do their magic.
- On first and second blush, the newly transformed stem cells look and act like Pleuripotent Embryonic Stem Cells (the real McCoy).
- But this remains to be seen, many a grant and paper are yet to come.
So don't get all wound up thinking you can inject this stuff into you and magically turn 16 again. Remember, you can only be young once.
But you can be immature forever.
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24 would work for me, thanks.
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Oh quit being such a downer.
It IS a big deal because it is another small step towards me being able to grow my own replacement organs.
Every tiny step we take towards that goal is exciting.
When we reach the stage where we can grow replacement organs which will have no rejection problems we will be able to add *decades* to our lifespans. It will be the greatest advance since antibiotics.
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So don't get all wound up thinking you can inject this stuff into you and magically turn 16 again.
I can't dream up any reason how you can read that into anything I said. My analogy, if you will, is more along the lines of, when it DOES work, access isn't restricted to the highest bidder. Otherwise what you will have is similar to the shooting victim being denied pain killers because he's not insured.
Re:Obstacles?? OBSTACLES??? (Score:4, Insightful)
But to brighten your day perhaps - an important subtext of this research is how easy it is to get to what appears to be pluerepotent stem cells. Four proteins. Already three different techniques [nature.com] to get these into cells. Published research that others ought to be able to reproduce. Not only in this patent crazy country but everywhere else that has the infrastructure to do this kind of research. Which is relatively easy - certainly doesn't need any fancy expensive physics package like the LHC. IF medical therapies come of this line of research, it will be broadly known and likely broadly copied.
Stay tuned.
ON BEING YOUNG AGAIN (Score:2)
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With W gone, I don't see any.
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You are aware that it went a little further than that aren't you? The block was extended to using anything that had ever had Federal money used on it. So if you used part of a prior grant to equip your lab for different research you had to scrap it all and start again. You couldn't even buy used equipm
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What is wrong with using a miscarried fetus for the cells? How is that any different than havesting organs from a miscarried baby for transplants? Should that fetus/baby die in vain when it could save lives?
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Adult stem cells is the answer. (Score:3, Informative)
Though fetal stem cells (taken from aborted fetuses) may be useful for research, organs grown from them cause severe rejection in the recipient of the transplant.
The only way to overcome this rejection is to grow the organs from the adult stem cells taken from the recipient herself.
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'Only' is a pretty strong word there.
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The only way to overcome this rejection is to grow the organs from the adult stem cells taken from the recipient herself.
Unless we clone the patient and get embryonic stem cells from the clone.
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And to clone a person you'd need a stem cell to begin with..
No, all you'd need is any adult cell from the patient and an egg cell from any donor - no adult stem cell needed (unless you count the egg cell).
So that "embryonic stem cell" would be created from the adult stem cell..
No.
Re:Adult stem cells is the answer, Well maybe not. (Score:1)
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The technical term is somatic cell nuclear transfer. (Don't worry, it has nothing to do with plutonium.)
Ha! That's gold. I've never seen a more subtle way to tell someone that you think they're a moron.
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The idea is that you'd make a new embryo but use the DNA from whomever the patient was. ... You'd hopefully get embryonic stem cells that wouldn't get rejected.
Isn't that pretty much what I said?
Of course the pro people would have to come up with a new talking point they could use endlessly while the anti-abortion people would flip out over murdering babies.
An actual treatment based on embryonic stem cells would certainly change the terms of the debate, but isn't that irrelevant as to whether or no
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Though fetal stem cells (taken from aborted fetuses)
Foul! ESC aren't taken from aborted fetuses, they're taken from in vitro fertilization wasted embryos: embryos that were bound for the trash, not on their way to being born. Abortions never were used for embryonic stem cells: those fetuses had already used up their pluripotent stem cells.
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Though fetal stem cells (taken from aborted fetuses) may be useful for research,
Haha.. you fell into the Conservative lies.
It's called embryonic stem cell [wikipedia.org] technology because the stem cells come from embryos. We're talking no more than 50-150 cell bundles here. But some people believe that "life starts at conception" and, to them, that means any fertilized ovum should be carried to term. They encourage people to adopt frozen embryos and call the babies that result "snowflake children". Of course, the vast majority of frozen embryos are not adopted (and it would be completely impract
Or to modify the histamine complex on chromosome 6 (Score:2)
"The only way to overcome this rejection is to grow the organs from the adult stem cells taken from the recipient herself."
Or to modify the histamine complex on chromosome 6.
-- Terry
That's nothing! (Score:5, Funny)
You should see the stuff that grows on MY dishes!
What a shame (Score:3, Interesting)
Yes, folks, that's sarcasm that will undoubtedly be confused with flamebait.
Depends (Score:3, Informative)
It depends what you mean. Stem cells are being used for a variety of therapies at the moment. If you mean growing complete organs then you probably have a while to wait. It's one thing to grow some cells in a petrie dish and quite another to convince them to organize into, say, a heart.
Of course stem cells can be grown in a petri dish! (Score:4, Informative)
The innovation here is that they have a new approach to transform the cells into stem cells that may be safer than previous alternatives. For example, gene therapy commonly relies on viral vectors to insert genes to produce the proteins into the genome. However, because these insert randomly, they can inactivate genes involved in cell proliferation regulation etc. resulting in cancer. There are other approaches such as naked DNA transformation, but then the genes producing the proteins are generally not replicated or segregated evenly when the cell divides and are thus lost over successive divisions.
What these people have done, is to avoid all the usual problems by making the required proteins (already well known) for cell transformation in a bacterial system and adding a seqeuence to them that produces a cell penetrating end - similiar to that found in some viral proteins. This allows their proteins to penetrate the cells and activate pathways that inactivate/activate certain genes sets to make the cells pluripotent. These changes appear to be permanent and hold for over 35 passages.
As a side note, this is a burgeoning field of research. The efficiency and efficacy of certain protein products as above, and even genetic material, can be greatly enhanced by the addition of nuclear localisation sequences, certain histones and so on, without nasty side effects.
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The factors are not made in a bacterial system BTW. They are expressed in HEK293 (derived from human embryonic kidney) cells and the cell extract used.
Stem cells are not a cure (Score:2, Informative)
Stem cells are a treatment technology, or may lead to one. One of the likely targets for therapy is to replace lost cells in the substancia negra in the brain that occurs in Parkinson's disease. Having the stem cells means you have to induce them to develop into s-n types cells, find a way to put them into the center of the brain, avoid immune responses if any and infection from the operation. It would also be nice to see the new cells did not become malignant or die quickly due to the same things that caus
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A researcher on a panel discussion part of the NYC PD Unity Day events guessed less than 10 years.
They said that 10 years ago. The MJF Foundation will apparently close down in another 10 years time if a cure is not found.
Scientists growing scientists in petri dishes ... (Score:5, Funny)
. . . now *that* will be cool!
. . . or, maybe not?
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Oblig (Score:1)
Human Lifespan? (Score:1, Interesting)
If we can easily swap decaying/dead organs for fresh ones, How long will the average human live? Today it's generally seen that you can easily live 100 years or more, but people with fresh new organs? What of the mind? I wonder where this will lead for future developments.
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I remember reading somewhere sometime that the rejuvenated human body could subsist for 200K years+...Unfortunately, I have no links or empirical data to back that up, so take it for what it is, essentially heresay, but it is thought provoking....
Given that most of us can't remember what we were doing 200k seconds ago, is living 200k years any different than living 200?
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Oblig. XKCD (Score:3, Funny)
Breakthrough yet to be optimized (Score:4, Informative)
Clever idea (Score:5, Informative)
There is more to this than it is published in the paper. You can use the same trick to push your newly obtained iPSC to differentiate into the cell type you need. For example introduction of MyoD can turn them into muscle cells for treatment of muscular dystrophy.
FDA Hurdles (Score:3, Insightful)
Everything Gives You Cancer (Score:3, Informative)
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The hard part is differentiating them into the tissue that you want -- safely.
I bet epigenetics and cell memory will have a crucial role here. Genome wide studies showed that many PcG and TrxG genes change their expression levels during differentiation. Also, i find idea of bivalent chromatin to be very attractive - a cell has histone marks that can either silence or activate genes and depending on the context it will be tilted hopefully the "correct" way.
Of moderate importance (Score:4, Informative)
Creating stem cells from adult cells is so far mainly interesting for research purposes. The first hope of researchers is that in the petri dish, culture flask or microtiterplate, stem cells and stem cell derived cell lines may be better research tools than the current cell lines. The cell lines currently used in laboratories are often cancer cell lines and poorly representative of the cells in someones brain or liver. Stem cells may also help us to better understand cell development and what happens when it goes awry.
For therapeutic applications, the first applications may depend on finding drugs that stimulate stem cells to differentiate: It may not be necessary to inject stem cells or cell derived from stem cells, because we may all carry cells with a differentiation potential. For example, regions of the brain seem to contain cells that could potentially differentiate to help people who are suffering brain damage or degeneration.
However, controlling differentiation is complex. While only four factors are sufficient to induce any cell to revert to a stem-cell state, inducing a stem cell to become e.g. a motor neuron is a very complex process that needs to be controlled step by step.
So... (Score:3, Insightful)
...this is GOOD news for everyone, right?
The people who demanded stem cells research be funded by the government (it was never banned, despite the rhetoric of the Left), now they will be able to gather as many stem cells as they want to follow any potential lead in terms of therapies.
The people who had moral qualms about the circumstances of gathering stem cells and the potential for abuse will be able to rest easy that there is NO moral context in the harvesting of petri-originated stem cells.
I know it's really, really hard not to fling poo at each other (if only from habit) but can we all agree this is a good thing?
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I agree it's great news ever since "The Simpsons" made a joke about "stem cell fajitas". I'm starved.
Seriously though, it sounds like there's great potential here. I always thought embryonic stem cells would end up being a dead end, and not just for the moral reasons. It makes much more sense to me if you can do something with adult cells, especially if they come from the person to be treated.
Of course, I don't know squat about the biology involved, but common sense dictates making a cure from the cells
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> (it was never banned, despite the rhetoric of the Left)
Too young to remember back that far? It was "not a ban" in the same kind of way that Microsoft is "not a monopoly". It effectively immediately killed research, because a company doing work on embryonic stem cells (except a few lines that turned out to be completely useless due to contamination) couldn't receive any federal funding for anything else at all. This covered every organization at the time that was willing and able to do that research. It
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...this is GOOD news for everyone, right?
The people who demanded stem cells research be funded by the government (it was never banned, despite the rhetoric of the Left)
So, given the way that it was set up to ban any kind of cross-use of funding (including buying stuff that could potentially have been previously funded by the public) and blocking funding to different projects by the same companies, and given the large proportion of research funding in the US that is from the US government, let's agree that you'll use the term "effectively banned", to counter your bias against it being "banned", and I'll use the term "funding removed including funding of different projects
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Please.
You claim 'effective banning' yet it wasn't banned in ANY other country, it wasn't banned from the funding of private foundations (who have $billions themselves), it wasn't banned from STATE funding (as I recall California was ponying up $billions as well).... ...and where are all the therapies?
EVERY OTHER COUNTRY IN THE WORLD could pursue this 'miracle' cure for everything from the common cold to cancer, yet *somehow* since the US refuses to fund it with federal dollars, it's "banned"?
Personally, I
Hints & dDirections (Score:1)
I'm sorrowful. Sorrowful because of earlier comments. Is it really big achievement to read short paper and then write review of "Brief Report"? Nevertheless slashPOTTERS! The idea is quite old. Thomson et.al. described this idea in this paper: http://www.sciencemag.org/cgi/content/abstract/318/5858/1917 [sciencemag.org] . There are earlier, but this one is good one and representative too.
I suppose that questions about possible mechanism come from ignorance and laziness. Partially answer can be found here :http://images.cel
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I'm sorrowful. Sorrowful because of earlier comments. Is it really big achievement to read short paper and then write review of "Brief Report"?
Actually ./ readers don't know each other so nobody gives a shit about other user's personal feelings unless they're expressed in an amusing way. Try to comment on the very gist of discussion and not on the people unless you want to be on the fast track to flamewarz.
he idea is quite old. Thomson et.al. described this idea in this paper: http://www.sciencemag.org/cgi/content/abstract/318/5858/1917 [sciencemag.org] [sciencemag.org] . There are earlier, but this one is good one and representative too.
The idea is old and everybody who read paper cited in the story knows that, but here reprogramming is epigenetically-triggered, i.e., there's transduction of proteins, not genetic material by viral vectors.
We are commenting on brief review
ReCell (Score:2)
You may be interested in this:
http://www.avitamedical.com/?id=5&ob=1
It is a leading product in regenerative therapy and was used on the victims of the Bali Bombings way back when.
maybe not so fast (Score:1)
Actually ./ readers don't know each other so nobody gives a shit about other user's personal feelings unless they're expressed in an amusing way
Yes, maybe that's right. But based on some comments I almost sure about some level of capabilities of some writers.
The idea is old and everybody who read paper cited in the story knows that, but here reprogramming is epigenetically-triggered, i.e., there's transduction of proteins, not genetic material by viral vectors.
You have not understood me. I ment that the idea of reprogramming is quite old. If you prefer (please read slowly! ) generall idea (making iPSCs by virial vectors) is : VERY OLD in scientific scale of time. If readers of this paper look deeply into references of this, they will see that's true.
We are commenting on brief review because of it's briefness. Remember that you have only ~20 minutes for writing significant contribution, after then your post will be placed in the tail of the discussion, chances for never being moderated. Thus, comprehensive posts can be written if someone's already expert in the field, no time for quick literature search.
So why are you comment story? If you are not experts ,please read more papers, then become an expert