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You are here: Home / Science & Technology / Skin Cells To Stem Cells

Skin Cells To Stem Cells

by Tim F|  November 20, 200710:25 pm| 18 Comments

This post is in: Science & Technology

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Cool.

Scientists have managed to reprogram human skin cells directly into cells that look and act like embryonic stem (ES) cells. The technique makes it possible to generate patient-specific stem cells to study or treat disease without using embryos or oocytes–and therefore could bypass the ethical debates that have plagued the field. “This is like an earthquake for both the science and politics of stem cell research,” says Jesse Reynolds, policy analyst for the Center for Genetics and Society in Oakland, California.

Since the key concept behind this was reported for mice in June, “earthquake” strikes me as overstating the case a bit. Translating the mouse tech to human cells is an engineering problem, and not a very challenging one at that.

On a practical level Kevin Drum argued that no technique involving virus DNA transfer will be approved for people. Given the discouraging rash of patient deaths gene therapy I can see his point, but for two reasons I think that he’s off the mark on this one. First it’s important to note that even patient deaths have only put gene therapy on hold rather than killed it. Stem cell therapy has already produced astonishing medical advances, which is nothing compared to the magic tricks like limb and brain injury regeneration that researchers feel increasingly confident in promising. If deadly viruses can’t kill gene therapy outright then the stiffer wind at the back of stem cell treatment will keep clinical work moving forward.

Second, I doubt that the debate will even be necessary. I will drop in details after the break, but suffice to say that tech exists to do virus cloning without worrying about down-the-road infectivity.

How’s that, you say? Biologists trying to shuttle genes often use a two-stage virus trick that retains the monster DNA transfer rate of viruses but never produces a “live” virus capable of copying itself in a host cell. The two parts of this trick are (1) a “packaging” line of mammalian cells that produces the virus coat proteins but no virus DNA, and (2) a stretch of external DNA (a plasmid) containing the gene that you want to shuttle around plus some extra sequence that fools the virus coat into packing the plasmid inside as if it was the virus’s own DNA. Slip the external DNA into the packaging cell line using old-fashioned non-virus techniques and the cells will start to produce “viruses” that shuttle DNA just as well as wild adenoviruses, but instead of virus DNA they insert whatever gene you designed them to carry. Without virus genes the host cell will never produce new virus particles.

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18Comments

  1. 1.

    demimondian

    November 20, 2007 at 10:34 pm

    Yah…but, um, Tim? Did you look at the list of genes they inserted?

    sox-2. c-Myc. c-Myc! The mother of all oncogenes.

    Not a chance in hell that I’d play with the fire, man.

  2. 2.

    Tim F.

    November 20, 2007 at 10:42 pm

    Demi, that’s what animal trials are for. Agreed 100% that viruses with oncogenes are bad news to the nth power (I could tell stories…), but research increasingly points to stem cells at the center of most cancers anyway. In some ways playing with stem cells is already playing with cancer.

    However, if they just put c-Myc on a CMV promoter and it stays on after the cells try to differentiate, well, the entire approach is a dead letter and that’s that.

  3. 3.

    TenguPhule

    November 20, 2007 at 11:15 pm

    They sure as hell better regulate the bejeezus out of this, we don’t need a real life hollywood schlok medical disaster on our hands with everything else on the plate.

    The tech may exist Tim, but the people pushing for products on the shelf are well known for cutting corners.

  4. 4.

    Knecht

    November 20, 2007 at 11:32 pm

    Wasn’t the issue with gene therapy not that the viruses were reactivating, but rather that the gene itself was integrating itself into naughty parts of the genome and messing up the regulations of various other oncogenes/messing with genomic stability?

  5. 5.

    Ranger3

    November 21, 2007 at 4:13 am

    So… when do we get jetpacks and flying cars?

  6. 6.

    Face

    November 21, 2007 at 9:10 am

    Wasn’t the issue with gene therapy not that the viruses were reactivating, but rather that the gene itself was integrating itself into naughty parts of the genome and messing up the regulations of various other oncogenes/messing with genomic stability?

    Exactly. Gene therapy will probably not succeed b/c the virus used tends to insert its DNA somewhat randomly (or at least, not accurately). This will frameshift the necessary genes and ultimately lead to some horrific cancers.

    Tim, how likely is it that an inserted plasmid will “hold”? I thought these things were quite unstable, especially in eucaryotic cells. The Caco-2 line I’ve worked with is notorious for losing the plasmid; is this “old-fashioned” technique just plain old transfection?

  7. 7.

    Salmon of Trout

    November 21, 2007 at 9:15 am

    Sorry Ranger3, George W. Bush would have invented those (as well as cure cancer) but he’s been too busy fighting with the Defeatocrat Congress.

    So go yell at Harry Reid. It’s all his fault.

  8. 8.

    Punchy

    November 21, 2007 at 9:58 am

    $100 says Bush vetos a bill authorizing this science. No logic, no reason, just sees the words “totipotent”, “stem cell”, and “research”, and vetos it.

  9. 9.

    Tim F.

    November 21, 2007 at 10:05 am

    Tim, how likely is it that an inserted plasmid will “hold”? I thought these things were quite unstable, especially in eucaryotic cells. The Caco-2 line I’ve worked with is notorious for losing the plasmid; is this “old-fashioned” technique just plain old transfection?

    There are basically two types of transfection. The transient kind involves shuttling a plasmid into the cytoplasm and, while much easier, only lasts a couple of days. People developing this therapy will certainly go for the stable kind of transfection, in which a batch of transients are screened over (and over and over and over) to isolate the small number that integrate the plasmid into their genome. Unless you’re working with a cell line with ploidy issues and genomic instability (HeLa) the stable insertion is pretty stable.

    Awkward insertions (e.g., into a Ras transcriptional repressor) are much easier to deal with here than in gene therapy because you can screen the stem lines to weed out the insertions you don’t want. I just don’t think that particular problem is an issue in this case.

  10. 10.

    Zifnab

    November 21, 2007 at 10:14 am

    They sure as hell better regulate the bejeezus out of this, we don’t need a real life hollywood schlok medical disaster on our hands with everything else on the plate.

    So long as we don’t release a strain of virus that turns everyone into flesh eating zombies. I freak’n hate zombies.

  11. 11.

    Evinfuilt

    November 21, 2007 at 10:32 am

    There are a couple points that need to be made here (or emphasized.)

    1. Currently these stem cells are liable to cause cancer on the poor mice.

    2. This is all so we can begin research stopped by Bush 6 years ago. So this break through is the sudden “back to 2000 tech” even though we’re still not there. How many potential stem cell uses could have been discovered over the past 6 years? All so Bush could say he’s protecting some embryo’s.

    3. Those embryo’s Bush was “protecting” just got tossed into the incinerator instead of being used for science. Good job Bush, you not only didn’t save them, you set back science 6+ years and left many people to die from potential cures. So I guess, judging by total number of deaths this isn’t his biggest screw up. Still Bush is taking personal credit for this “break through” which I think is great. As long as you look at the whole picture.

    Bush takes credit for putting science back 6+ years and lets countless people die.

  12. 12.

    jcricket

    November 21, 2007 at 11:01 am

    Having worked with enough cancer researchers to know how many promising breakthroughs turn out to be duds, I’ll withhold my enthusiasm.

    Not that they’ve made the breakthrough, but the enthusiasm that this means we don’t need to use embryonic stem cells for the same type of therapies these cells might be usable for.

    Of course, if in a couple of years these cells turn out (again) not to be as useful as ESC, we will still be back where we were in 2000.

    Hopefully the countries not run by religious nutcases will have advanced ESC research by then.

  13. 13.

    Punchy

    November 21, 2007 at 11:30 am

    Having worked with enough cancer researchers to know how many promising breakthroughs turn out to be duds, I’ll withhold my enthusiasm

    Ah yes…the bane of The Latins! The bumpy, often insurmountable transition down the In Vitro–>In Vivo–>In Situ road that derails nearly all of these projects.

    The ethics involved here are also extremely non-trivial. The fact that people have died in these studies leads me to believe that the actual in situ research will be the most complicated and watched in the history of clinical trials.

  14. 14.

    jcricket

    November 21, 2007 at 11:48 am

    I do like that they get the researchers to mention that GW Bush’s anti ESC funding stance has basically set this area of research back at least 5 years (and who knows how many lives lost)

    One of the researchers involved in yesterday’s reports said the Bush restrictions may have slowed discovery of the new method, since scientists first had to study embryonic cells to find out how to accomplish the same thing without embryos.

    “My feeling is that the political controversy set the field back four or five years,” said James Thomson, who led a team at the University of Wisconsin and who discovered human embryonic stem cells in 1998.

    The wingers will never get this, but they are the ones hurting progress in so many areas with their neanderthal (sorry caveman) stances. They hurt our ability to make progress in science. They hurt our ability to prosecute the war on terror (with unnecessary war and rendition limiting our ability to secure cooperation internationally on anything else).

    I really used to feel that there were two political parties, each with different opinions, but both fundamentally wanted what’s best for America. Now I’m pretty secure in the belief that there’s only Dems have America’s interest at heart. Republicans? I dunno what America they think they’re living in, but it ain’t mine.

  15. 15.

    Punchy

    November 21, 2007 at 12:13 pm

    Unless you’re working with a cell line with ploidy issues and genomic instability (HeLa) the stable insertion is pretty stable.

    “stable” is incredibly relative here, Tim. For cell lines, “stable” might be 50-60 passes. For an individual, that’s weeks/months. This would have to be an on-going therapy, I’d believe.

  16. 16.

    demimondian

    November 21, 2007 at 1:06 pm

    I don’t take _Science_ any more, so I haven’t read the M-and-M’s for Thompson et al. Surely someone who does (or whose reading room does — hint, hint, Tim) can just go look. The popular press suggested genomic integration by retroviral insertion, which is certainly believable given the low efficiencies obvserved, but I’d prefer to have data from someone who, like, read the paper?

  17. 17.

    Tim F.

    November 21, 2007 at 3:10 pm

    It’s published online and apparently inaccessible from my facility, so no can do.

Comments are closed.

Trackbacks

  1. Balloon Juice says:
    December 30, 2007 at 12:45 am

    […] Of course proof-of-principle is not exactly the same as an invisible plane. Take that astounding report that scientists could make embryonic-like stem cells out of ordinary adult skin cells. If that isn’t magic, right? There was some debate about the usefulness of the technique, which I deferred since the technical details were not available to me yet. […]

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