Making bone: Stem cells derived from skin are better at forming bone cells (right) than stem cells derived from blood (left) are, because skin is more closely related to bone. Colonies of bone cells are shown in red.
Kitai Kim, Children's Hospital

Biomedicine

Reprogrammed Stem Cells Remember Their Past

Engineered stem cells carry markers of their former identities--a trait that could hinder research into diseases.

  • Tuesday, July 20, 2010
  • By Lauren Gravitz

While reprogrammed stem cells--those derived from fully differentiated adult cells--can be transformed into any type of tissue, scientists have now discovered that they preserve a memory of where they came from. That memory appears to influence the cells' development; reprogrammed stem cells are more easily converted back to their original identity, according to a study released online today in Nature. The findings could affect research into the two main uses for reprogrammed stem cells; growing efforts to study disease in cells derived from patients with those diseases, and the development of replacement cell therapies.

A few years ago, researchers developed a way to reprogram adult cells into stem cells using a simple combination of genetic or chemical factors, no embryo required. Like embryonic stem cells, these induced pluripotent stem (iPS) cells can both reproduce themselves and differentiate into just about any type of tissue in the body. The technology spread rapidly around the globe, providing a way to study stem cells and their potential therapeutic benefits without the technical and ethical hurdles of using cells derived from embryos. But three years later, complications continue to crop up.

While iPS cells have passed all the traditional tests of so-called pluripotency--the ability to differentiate into any type of tissue--and appear genetically identical to embryonic stem cells, they do have limitations. George Daley and his colleagues have found, by studying stem cells from mice, that cells derived from blood are better able to differentiate back into blood cells than into bone; those derived from bone make poor blood cells and even poorer neurons.

Daley's team also compared mouse iPS cells to those that had undergone nuclear transfer, the technique used to clone Dolly the sheep. The two methods trigger different mechanisms to push a cell back to a stem-cell state, and the chemical methods of iPS cell reprogramming appear to be less thorough. The iPS cells maintain chemical modifications on their DNA indicative of their previous identity, while nuclear transfer wipes the slate clean. (It wasn't possible to do similar experiments with human cells, because no one has yet cloned human cells.)

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The findings create a snag for the use of iPS cells for basic disease research. Many scientists have been collecting skin samples from patients with various diseases, reprogramming them back to iPS cells, and then prompting them to differentiate into tissues affected by the disease. This allows them to examine how the disease unfolds at a molecular level. But if the disease is a neurologic one, such as Parkinson's, or anything not related to skin tissue, the variation that occurs due to the originating tissue could mask effects of the disease.

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rhansing

74 Comments

  • 569 Days Ago
  • 07/20/2010

stem cells

That's the problem, what looks like a bona fide stem cell, is still not a bona fide stem cell, there needs to be a second step, perhaps more, to create one.

Alas, In time, I do expect the problem will be solved. It's just going back further, perhaps only one more step.

This is still one reason why we still need embryonic stem cells, to solve this problem.  Alas, this creates the religious debate…

Ethically, I personally feel that unused donated embryos with proper consent, is the way to go. What else will one do with unused embryos… keep them in liquid nitrogen, forever? Regardless, full disclosure policy should be followed.

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karencole37

2 Comments

  • 561 Days Ago
  • 07/28/2010

Re: stem cells

You know what you are talking about. Me, I have a blog on Google Blogger and am trying to feature the top stem cell news there: http://stemcellresearchissues.blogspot.com/
I used to hands on work with the disAbled. Anyway, I know now that fetal stem cells are needed for people with genetic disabilities and illnesses, and we need adult stem cells for those who are not genetically afflicted, including those with cancer-prone tendencies, such as myself and my family. So I favor adult stem cell research, as it's better for those with cancer, I think, and also favor fetal stem cell research, as well as umbilical cord stem cell research, as it involves people with needs other than mine. So far as I am aware at this point anyway.

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Asclaepius

53 Comments

  • 566 Days Ago
  • 07/23/2010

Genetic Nostalgia

knowing from the get-go that a ban of cloning heralded the return of the inquisition, let me assure you, as a rational, law abiding individual I am also 100% against cloning, but only after we understand and learn to replicate the cloning  mechanism(s.)  Shutting the door on scientific truth seekers, working to better the lot of mankind is a moral, ethical abomination.  Let me tell you why using this article as a reference point.

embryonic stem cells are imbued with an abundance of copiousness, they have a lot of growing to do, evolving from one cell into a multimillion cellular adult organism....reprogramming an adult cell into a look alike phenotype induced pluripotent stem cell is doable either through chemical or atomic baths, but "Houston we have a problem here" these iPS cells and their enviable ability to reprogram and reproduce themselves into any kind of tissue, have a tendency to revert to their previous state of being thus researchers as the article points out, find iPS cells not as helpful as they could be  in laboratory understanding disease states being examined. What's happening?

Researchers doing a little bit of backtracking, confirming, replicating the 3 billion DNA letters encoding the human genome blueprint are finding transposable elements of genetic resource material, handed down to us through highways and  byways of heritage and heraldry, previously thought to be inert starstuff, just hanging around our genome.   These elements start acting like wild cards, making copies, snippets of themselves and showing up unannounced hither, dither and yonder different places in our genome.

When genetic variants show up in laboratory petrie dishes, genetic essays unexpectedly, they blow researchers minds, frustrating efforts to induce adaptive compliance on lines of reconstructed stem cells in new tissue neighborhoods; instead of helping find out what's wrong, the stem cells nostalgically revert back to their previous self, spiting our best intentions.
As JV Moran and collegues at the U of Penna point out "there is a strong possibility that retrotransposition occurs more frequently than previously thought".  The presence of wild card elements copying their RNA and inserting it in other chromosome locations, altering our genomic  DNA structure for good, bad or other unknown variables; may be a factor in stem cell genotype reversion.
There is also a curiosity as to whether a scaffolding structure, elusive deluxe, exists in our DNA helix.  The question we have been asking ourselves: whether a cell splits right down the middle at mytosis, or does it form a mirror template of itself in which cellular components split filling the new template into two mirror enveloped halves of the cell, same split of genetic material engulfed in nucleic membranes and distributed. 
Have we been here before?
Being mindful that the map of the human genome is a fairly recent phenomenon, imagine if you will the accuracy of Lewis and Clarke's maps.  Fifty years later mountain men decimated beaver populations, waterways would have changed course, a century later,telegraphs, railroads a vast improvement with noticeable significant accuracy; today with GPS cartography use of maps a user friendlier, practical more convenient experience.
The human genome just got here, understanding cloning would help get by logjams as outlined in the article above.
Our ingenuity to surpass obstacles is being challenged, the ban on the study of cloning almost seems like someone is tying one of our hands behind our back.  The lawfully mandated inaccessibility to growth factor laden  stores of genetic reserves in embryonic stem cells may cause us to skip a step now and then, maybe even stumble once in a while, but we're on the way.
        

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karencole37

2 Comments

  • 561 Days Ago
  • 07/28/2010

Re: Genetic Nostalgia

Dear My that was very long,

Let's be brave
Let's be true
To the red, white and blue
Let's experiment on mice and people

Let's be weird
Let's be gay
Let's be any old way
And ignore that blood-coated church steeple.

Yrs,

Karen

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