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Biotech Science

Scientists Demonstrate Mammalian Tissue Regeneration 260

telomerewhythere writes "A quest that began over a decade ago with a chance observation has reached a milestone: the identification of a gene that may regulate regeneration in mammals. The absence of this single gene, called p21, confers a healing potential in mice long thought to have been lost through evolution and reserved for creatures like flatworms, sponges, and some species of salamander. 'Unlike typical mammals, which heal wounds by forming a scar, these mice begin by forming a blastema, a structure associated with rapid cell growth and de-differentiation as seen in amphibians. According to the Wistar researchers, the loss of p21 causes the cells of these mice to behave more like embryonic stem cells than adult mammalian cells, and their findings provide solid evidence to link tissue regeneration to the control of cell division. "Much like a newt that has lost a limb, these mice will replace missing or damaged tissue with healthy tissue that lacks any sign of scarring," said the project's lead scientist.' Here is the academic paper for those with PNAS access."
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Scientists Demonstrate Mammalian Tissue Regeneration

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  • Re:So (Score:5, Informative)

    by TheMeuge ( 645043 ) on Wednesday March 17, 2010 @11:31AM (#31509134)

    I have a feeling you should know something about the subject before weighing in.

    p21 knockout mice don't appear to get cancer more than wild-type mice, interestingly enough...

    It's interesting, because p53 is a major regulator of p21 expression, and p21 itself is a major player in regulating cell cycle progression into S-phase, thus controlling cell replication. p53 knockouts, on the other hand, are extremely prone to cancer, as p53 is one of the most important tumor-suppressor genes.

    The paper is interesting because the authors demonstrate that two separate strains of mice that contain a p21 deficiency can both regenerate differentiated tissue (measured by looking at ear-hole closure), supporting the link between p21/cell cycle progression and tissue regeneration. Whether this is of consequence therapeutically is a different story, but I'd be very interested to see the same study repeated in wild-type mice being fed or injected a small molecule p21 inhibitor.

  • What's the downside? (Score:5, Informative)

    by Biotech9 ( 704202 ) on Wednesday March 17, 2010 @11:36AM (#31509204) Homepage

    A lot of people are asking why evolution has taken away our regenerative capacities, and are guessing what the downside of this regeneration is.

    P21 is involved with anti-cancer. It arrests the cell cycle when DNA damage occurs, allowing the damage to be repaired (so mistakes are not carried forward into new generations). Or if the damage is too severe, the cell is made senescent (they lose the ability to reproduce and instead lead out a gentle retirement, performing their normal job until they just die of old age)

    P21 knockout mice show a lot of carcinomas and P21 is also up-regulated by and works to remedy excessive oxidative stress. It's very unlikely this research is going to lead to a pill that knocks out P21 and lets us grow limbs back. It will only lead to a greater understanding of how our pathways work.

  • caveat (Score:5, Informative)

    by TheMeuge ( 645043 ) on Wednesday March 17, 2010 @11:38AM (#31509230)

    Of course the caveat to using mice to judge how a gene affects long-term development of cancer is that there really is no "long-term" on a human scale in mouse studies, since they only live about 3 years at most.

    I'm also not entirely familiar with the effect of p21-deficiency in cases where major tumor suppressors are deregulated or otherwise deficient. It is feasible that in the absence of further regulation, the absence of a major cell cycle checkpoint will lead to a more severe phenotype, whether in terms of being more tumor prone, or development of more aggressive tumors.

  • by serialband ( 447336 ) on Wednesday March 17, 2010 @11:45AM (#31509326)

    Isn't this the backstory to the Lizard? He tries to regrow his arm using amphibian DNA, and whoops - he turns into a Lizard.

    Hm, it sounds really stupid now that I've typed it out.

    Lizards are reptiles.

  • Re:caveat (Score:4, Informative)

    by egomaniac ( 105476 ) on Wednesday March 17, 2010 @12:05PM (#31509638) Homepage

    Primarily because they are cheap to breed and raise, take up very little space, reach maturity quickly, and people usually don't freak out about experiments on mice the same way they would on (say) primates.

    They are also an acceptable human analogue in that they generally respond to medication and treatments similarly to how a human would; there are certainly other animals which are better models, but there are logistical, economic and public relations issues with trying to keep hundreds of chimpanzees in order to punch holes in their ears.

  • Promissing but... (Score:3, Informative)

    by Corson ( 746347 ) on Wednesday March 17, 2010 @12:21PM (#31509880)
    It is unlikely that a process so complex as mammalian tissue regeneration be controlled by a single gene. Moreover, p21 mutations have been associated with cancers. Which brings forth another question: why is it that only "lower" organisms (and mammalian fetuses) are capable of scar-less tissue regeneration? The answer is yet to be discovered but it is very likely that evolution had to stroke a balance between cancer control and tissue regeneration. It won't be easy to figure out "the way back" to regeneration, or even to avoid the risks of such a path.
  • Re:So (Score:3, Informative)

    by jimbobborg ( 128330 ) on Wednesday March 17, 2010 @12:22PM (#31509914)

    However, his healing factor results in massive scar tissue causing his appearance to be severely disfigured.

    No scarring with this stuff.

  • Re:I for one... (Score:3, Informative)

    by tmosley ( 996283 ) on Wednesday March 17, 2010 @12:28PM (#31510004)
    Ummm, the ability to regenerate lost body parts doesn't make you immortal. It just makes it less likely that the loss of an arm or a leg will end your life.
  • Re:I for one... (Score:3, Informative)

    by CharlyFoxtrot ( 1607527 ) on Wednesday March 17, 2010 @12:39PM (#31510254)

    Well, they claim that they thought it was "lost to evolution"... I assume the fact that the gene is not active today is the result of evolution. So that implies the question Why is it inactive? I would think the ability to regenerate body parts on demand would be an evolutionary advantage, wouldn't it?.

    Supposedly around 8% of human DNA was inserted by viruses [] into our genome. It could be that a virus in the past messed up our ancestor badly enough to lose regeneration and killed of all the rest. Also evolution doesn't have a "goal" our non-regenerative ancestor was just lucky that through some trait it was the best adapted to the environment at the time and it survived. It doesn't mean regeneration had a negative side to it.

  • by bzdyelnik ( 1600135 ) on Wednesday March 17, 2010 @01:13PM (#31511012)
    The wikipedia entry for p21 ( is somewhat misleading about its relationship with cancer. For a good review, see: [] Excerpt: "However, p21-null mice were found to be more susceptible to chemically induced tumours of the skin (Ref. 94) and colon (Ref. 95), and following irradiation they displayed increased tumourigenesis and metastases (Ref. 96). In addition, using different mouse strains, others have found that p21-null mice exhibit spontaneous tumour formation in the background of other genetic knockouts, such as Muc22/2 (lacking mucin 2) (Ref. 97) and Apc1638/2 (carrying a mutant allele of the adenomatosis polyposis coli gene) (Ref. 98). Furthermore, subsequent to the initial description of p21-null mice, investigators have found that p21-null mice bred on a 129Sv/ C57BL6 50:50 background did in fact develop spontaneous tumours at an average age of 16 months (Ref. 99). Collectively, these mouse studies demonstrated the importance of p21 in mediating the G1 checkpoint, and its ability to function as a tumour suppressor."
  • by Anonymous Coward on Wednesday March 17, 2010 @01:15PM (#31511066)

    Silly Slashdotter! Didn't you know? Everyone else knows! I repeat the common knowledge here.

    DOGS HAVE OWNERS, CATS HAVE STAFF! ...all righty then...

  • Meeces (Score:2, Informative)

    by ThatsNotPudding ( 1045640 ) on Wednesday March 17, 2010 @01:19PM (#31511132)

    ...since they only live about 3 years at most.

    Somebody's never watched The Green Mile.

"Call immediately. Time is running out. We both need to do something monstrous before we die." -- Message from Ralph Steadman to Hunter Thompson