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Topic: Scientists 'reprogram' skin cells to behave like stem cells (Read 771 times) |
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letheomaniac
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Scientists 'reprogram' skin cells to behave like stem cells
« on: 2009-03-08 12:28:12 » |
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[letheomaniac] This is rather sci-fi...
Source: http://www.reuters.com/article/scienceNews/idUSTRE5247ZV20090306
Author: Will Dunham
Dated: 5/3/2009
Scientists remove cancer genes from stem cells
WASHINGTON (Reuters) - Scientists have taken another important step toward using ordinary skin cells that are made to behave like embryonic stem cells to find treatments for conditions like Parkinson's disease.
Researchers at the Whitehead Institute for Biomedical Research in Massachusetts removed a stumbling block in using so-called induced pluripotent stem cells, or iPS cells, by taking out potentially cancer-causing genes.
Writing in the journal Cell on Thursday, the scientists said they then turned these iPS cells into brain cells involved in Parkinson's disease.
The iPS stem cells could be made from a patient's own skin cells, reducing the chances that the body's immune system might reject the cells as it sometimes does with organ transplants.
Transplanting healthy cells made from iPS cells to replace cells damaged by disease or injury may be possible in the future. But a more immediate use for these cells may be in lab dishes testing the effects of new drugs, according to Dirk Hockemeyer, one of the Whitehead Institute researchers.
"For transplantation applications, we are further away," Hockemeyer said in a telephone interview.
Scientists have learned that just a handful of genes can reprogram a cell back to a state in which, like an embryonic stem cell, it can generate any type of cell in the body.
But these genes have the potential to cause cancer, and also may interact with unpredictable results with thousands of other genes in the cell, the researchers said.
The Whitehead Institute team used viruses to transfer three genes into the skin cells of Parkinson's patients, then removed them after they had done their job.
The result was a batch of cells that looked like embryonic stem cells from Parkinson's patients, without the extra genes.
They then used the resulting iPS cells to create dopamine-producing nerve cells. They are the brain cells that die in people with Parkinson's, causing telltale symptoms such as tremors, slow movement and balance problems.
It is the first time scientists have created human iPS cells that have kept their embryonic stem-cell-like properties after the removal of reprogramming genes.
"Other labs have reprogrammed mouse cells and removed the reprogramming genes, but it was incredibly inefficient, and they couldn't get it to work in human cells," Whitehead Institute scientist Rudolf Jaenisch said in a statement.
"We have done it much more efficiently, in human cells, and made reprogrammed, gene-free cells," Jaenisch added.
The DNA of the iPS cells ended up as nearly identical to the DNA of the original skin cells, the researchers said.
(Editing by Maggie Fox)
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Fritz
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Re:Scientists 'reprogram' skin cells to behave like stem cells
« Reply #1 on: 2009-03-08 15:03:21 » |
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Given that I don't understand the technology here, it looks like I may be able to live forever and get really proficient at screwing up my life and relationship 
Like [BL] notes on other topics; "I feel my tail getting all bushy" over the iPS cell stuff.
Cheers [letheomaniac], interesting.
Fritz
Source: Ouroboros
Author: An aged post-doc
Date: February 26, 2009
Functional telomerase is required for functional iPS cells
Since the first report of induced pluripotent stem cells in 2006, the field of regenerative medicine has been buzzing about the potential for such cells to provide a source of cells that avoid the ethical minefield that plagues the use of embryonic stem cells.
The original paper demonstrated that simply over-expressing four “reprogramming” factors (4F) allowed reprogramming of differentiated mouse and human cells into iPS cells, but a thorough characterization of the resulting cells is still underway. iPS cells exhibit telomerase activity (as do ES cells), but whether this is sufficient to restore telomere length, or if telomeric chromatin acquires ES-like characteristics, remains unclear.
To address these issues, a team led by Maria Blasco generated iPS cells using either the standard 4 factors (4F), or omitting cMyc (3F), from wild-type and telomerase-deficient mice (both young and old), and investigated various aspects of telomere dynamics:
Telomeres Acquire Embryonic Stem Cell Characteristics in Induced Pluripotent Stem Cells
Telomere shortening is associated with organismal aging. iPS cells have been recently derived from old patients; however, it is not known whether telomere chromatin acquires the same characteristics as in ES cells. We show here that telomeres are elongated in iPS cells compared to the parental differentiated cells both when using four (Oct3/4, Sox2, Klf4, cMyc) or three (Oct3/4, Sox2, Klf4) reprogramming factors and both from young and aged individuals. We demonstrate genetically that, during reprogramming, telomere elongation is usually mediated by telomerase and that iPS telomeres acquire the epigenetic marks of ES cells, including a low density of trimethylated histones H3K9 and H4K20 and increased abundance of telomere transcripts. Finally, reprogramming efficiency of cells derived from increasing generations of telomerase-deficient mice shows a dramatic decrease in iPS cell efficiency, a defect that is restored by telomerase reintroduction. Together, these results highlight the importance of telomere biology for iPS cell generation and functionality.
The key findings were (1) in telomerase-competent cells, telomere lengthening occurs via telomerase extension (rather than via a recombination), and (2) telomeric chromatin acquires ES-like characteristics. Furthermore, cMyc (one of the original 4 transcription factors used to generate iPS cells ) is dispensible for telomerase activation in mouse iPS cells (telomerase activity was only marginally lower in the absence of cMyc).
The authors also derived iPS cells from telomerase-deficient G1 (first generation) mice. It became clear that while telomerase activity is not limiting for in vitro iPS cell proliferation when telomeres are long (as is the case in G1 mice), these cells were nonetheless severely impaired in their ability to generate viable mice. Furthermore, the efficiency of iPS cell generation from telomerase-deficient G2 and G3 mice dropped significantly, indicating that telomere shortening is a critical barrier to iPS cell generation. Consistent with this, the cells exhibited an increased number of signal-free ends and chromosome end-to-end fusions, both events that are common in cells with very short telomeres. Crucially, re-introduction of telomerase into G3 telomerase-deficient mice restored iPS cell production efficiency, despite the cell inheriting short telomeres from their G2 deficient parents.
Overall, these findings highlight the role that telomere/telomerase dynamics play in successful iPS cell generation and provide evidence that cells from older donors are suitable. The caveat is that telomerase activity is vital if iPS cells are to be generated from cells with short telomeres. (Obviously!)
http://www.nature.com/nature/journal/v451/n7180/full/451858a.html
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letheomaniac
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Re:Scientists 'reprogram' skin cells to behave like stem cells
« Reply #2 on: 2009-03-09 03:29:43 » |
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Fritz:
Quote:Given that I don't understand the technology here, it looks like I may be able to live forever and get really proficient at screwing up my life and relationship
Like [BL] notes on other topics; "I feel my tail getting all bushy" over the iPS cell stuff. |
[letheomaniac] I too find this genetic engineering lark a bit untrustworthy. I'm in favour of cyborg upgrdes instead - give me hardware over 'cellware' any day! Still, if they do get it right it will be one less arrow in the quiver of the 'pro-life' nutters and so I think that I would have to say I'm in favour of funding research like this even if it is ultimately proved to be unviable. 
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MoEnzyme
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Re:Scientists 'reprogram' skin cells to behave like stem cells
« Reply #3 on: 2009-03-09 16:00:20 » |
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I'm not so sure what skin cells have to offer us now that the ban on embryonic stem cell research has been lifted. I suppose the sheer abundance and ease of collecting skin cells may have some remaining efficiency to the research, but in terms of real totipotency, nothing compares to actual embryonic cells. In fact I expect the remaining breakthroughs to occur with embryonic cells, where other cells might be engineered to bring the results more economically to the rest of the public.
I've started another thread on this: http://www.churchofvirus.org/bbs/index.php?board=5;action=display;threadid=42790
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I will fight your gods for food,
Mo Enzyme
(consolidation of handles: Jake Sapiens; memelab; logicnazi; Loki; Every1Hz; and Shadow)
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Hermit
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Re:Scientists 'reprogram' skin cells to behave like stem cells
« Reply #4 on: 2009-03-09 20:41:22 » |
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There is a critical difference Mo.
IPS is clearly simpler, and when sufficiently compatible donor cells are available, generic therapy using them is often be an attractive treatment path (e.g. repairing damage heart tissue by perfusing an IPS bearing solution directly into affected muscle), but if we can repair genetic cellular damage in vitro, including dealing with telomerase-deficiencies by converting the cells to pluripotent stem cells and use them for autoinnoculation, it is likely to make a much bigger difference to a large number of people, the vast majority of who do not have access to compatible stem cells. Particularly in cases of tissue necrosis and malignant tumours.
Kindest Regards
Hermit and Co
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With or without religion, you would have good people doing good things and evil people doing evil things. But for good people to do evil things, that takes religion. - Steven Weinberg, 1999
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