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Science

Human Limb Regeneration a Possibility? 50

Posted by michael from the organ-banks dept.
SablKnight writes "This NY Times article (free reg. req.) says maybe. Apparently research is being done in parallel with the more controversial stem cell implantation to attempt to regenerate missing parts in humans. Though this has been a subject of mild interest for centuries, serious research started much more recently, when an experiment involving mice suffered a setback. 'A few years ago, Dr. Ellen Heber-Katz, an immunologist at the Wistar Institute in Philadelphia, was conducting an experiment with those mice, which develop a disease similar to lupus. As is common, Dr. Heber-Katz punched a pattern of holes in each mouse's ear to so she could tell which mouse was which. Three weeks later, she said, when she checked on the experiment, 'there were no ear holes.'' A quick google search reveals similar stories about Dr. Heber-Katz' research in other publications, such as the Science Daily and Nature."
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Human Limb Regeneration a Possibility? More

Human Limb Regeneration a Possibility?

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  • stemcells (Score:2, Insightful)

    by virtualXTC ( 609488 )
    Correct me if I'm wrong, but I though the idea behind current stemcell research was regeneration with out having to "graft" any thing on, such as spinalcord regenaration. I wouldn't think it would be practical to try to graft a whole arm on, unless you sample the patients DNA and encode the stemcells with it to oppose rejection problems.
    • I think a lot of current stem cell research is pointing at taking a mass of stem cells, most likely not from the patient, and forcing them to differentiate into the desired organ in a lab environment. This would then be treated like any other organ donation, including immune system suppression to avoid rejection.

      The regeneration research here involvs more of a method of undifferentiating normal cells into stem cells where they are, which would avoid the whole rejection problem and surgery completely.

      SablKnight
      • I seem to remember a story about a newly discovered plastic-like material which was not unlike cotton wool. It's remarkable property was that, when a stem-cell/nutrient solution was added, the new cells would grow around the outside of the fibres. In one demonstration, the material was pressed into the shape of a human ear, and cartilage cells were added. In a few days, the cells had grown into a new ear, and the fibre scaffold had dissolved. I think many people remember the image of a mouse with an ear growing out of it's back.

        This is probably not new news to most people, but I wonder how many people knew that the same thing had been done with nerve cells. An experiment (sorry, no names or other pertinant details spring to mind at the moment) with mice showed that nerve cells can be regrown in-situ, and that further more, the new nerve cells actually connect themselves to existing cells.

        In the experiment, the took some mice and severed their spinal cords by removing 1cm of nerve cells. Then, they filled the gap with this fiber soaked in the nerve cell solution. Several days later, the mice had a rudimentary spinal cord and limited use of their hind legs. I don't know about anyone else, but this sort of thing makes me really optimistic about the future of medical science.

    • I wouldn't think it would be practical to try to graft a whole arm on, unless you sample the patients DNA and encode the stemcells with it to oppose rejection problems.

      When they are creating the stem cells (specifically from embryos), they take a nucleus from your own body and make a "clone" of you to grow from, then they can continue manipulating the stem cells to grow into the organ/organs they want.

      Just slapping on some stem cells on to the stub that used to be your arm doesn't do the trick...
      • Using nuclei from a differentiated cell in the cytoplasm of a stem cell kinda defeats the purpose of using stem cells in the first place.

        The primary difference between stem cells and differentiated cells is that in stem cells, no DNA has been "packed off". If you take a nucleus from a host adult cell, you have to unpack it, so to speak, to make it useful in the sense that you describe.

        It is more likely that you would make stem cells in that fashion, using unfertillized eggs as anucleate acceptors for the harvested, treated nuclei from the host.

        Unfortunately, cloning is illegal in the US. As is the use of human stem cells (except CA).

  • Heartless man grows a heart!
    Brainless child grows a brain!
    Stomachless woman grows an appetite!?!
  • Does anyone know how much research is going into a link between stem cells and cancer cells? IANAB(iologist) but the only major difference I can see is a lack of control in cancer. If we can find a way to turn on stem cells, maybe the same switch could work to turn off cancer?

    SablKnight

    • Re:Cancer link? (Score:4, Informative)

      by tid242 ( 540756 ) on Thursday September 26, 2002 @10:10AM (#4336489) Homepage
      If we can find a way to turn on stem cells, maybe the same switch could work to turn off cancer?

      Cancer is a very dynamic disease there is not, to the best of my knowledge, any way to just "turn off" cancer cells. The normal lifecycle of groups of cells consists of individual cells that "know" when to divide and when to die (aptoptosis), with cancer, cells may proliferate too rapidly, or cells, normal in all other respects, may simply not know when to apoptose. So there are many different facets of each individual cancer, and each patient with said cancer. For example: while some cancers may respond (by apoptosing) to genetic damage inflicted by cytotoxic chemotherapeutic agents, other cells may benefit from the mutation caused by said damage. Differnet cancers (and differnt populations of cancer cells in the same patient) may be driven by completely different mechanisms, especially as individual tumors evolve and adapt within their host, so again you'd be hard pressed to exact something from stem-cells that would/could just "turn it off."

      the term "Cancer" is actually a pretty generic term used to describe hundreds of distinct diseases, much as "Infection" doesn't really tell you the nature of each individual infection (bacterial, viral, fungal, protazoal, parasitic, etc, etc - what kind of bacterial? G-, G+, acid-fast, hemolytic, coagulase +/-, toxin-producing, etc etc.). So when you say "cure cancer" or "turn off cancer" it's like saying "curing infection."

      the only major difference I can see is a lack of control in cancer

      this, again, is an over-simplification. it's much like saying the only difference i see with infectious disease and commensulistic/symbiotic bacterial colonization (such as your intestinal floura, which can cause infection if cirumstances are such) is that with infection your immune system can't keep them in check and they're in the wrong place, and with colonization this is not the case... or in more Geek terms: "the only difference i see between a PDA and an ULTRA-SPARC machine is that the ULTRA-SPARC box is faster"-it's just a lot more complicated than that...

      Does anyone know how much research is going into a link between stem cells and cancer cells?

      Contrary (i think) to what you were asking by this question, there is a school of thought that ties the two together. There was a paper published a short while ago which hypothesised that aging is the result of cancer suppression, and the two are almost inseparable. In other words the body's loss of regenarative ability is due to its control of accumulating genetic defects of stem-cells... i had just skimmed the publication and am not sure about its validity, but an interesting idea nonetheless... draw whatever conclusions from this as you like, but as i said i'm not positive of the validity of this report...

      hmmm... that should be enough out of me :)

      -tid242

      • Thanks for the clarification, I wasn't aware of the many subtleties involved. I don't know a lot about the subject, but what I did remember was that tumors are basically caused by a group of cells spontaneously (or not) losing their restrictions on differentiation and reproduction. It seemed like a natural tie-in to stem cells, which also reproduce quickly (or they would have to for medical purposes at least) and are undifferentiated.

        I had heard of the link between aging and cancer before, but not in enough detail to tie that to stem cells.

        SablKnight
      • Contrary (i think) to what you were asking by this question, there is a school of thought that ties the two together. There was a paper published a short while ago which hypothesised that aging is the result of cancer suppression, and the two are almost inseparable. In other words the body's loss of regenarative ability is due to its control of accumulating genetic defects of stem-cells... i had just skimmed the publication and am not sure about its validity, but an interesting idea nonetheless... draw whatever conclusions from this as you like, but as i said i'm not positive of the validity of this report...

        Interesting idea, what journal was it in? I'd like to read it.

    • There is no real link... (Score:4, Informative)

      by tlambert ( 566799 ) on Thursday September 26, 2002 @01:11PM (#4338055)
      There is no real link there.

      Stem cells are cells which have arisen following gametogenesis. Cancer cells, in at least 80% of cases, are cells that have started production of telomerase independently. Stem cells do not have telomerase, which is normall present only during gametogenesis, and in cancers.

      A good company web site to look at to see how these things relate to each other, specifically dealing with oncology (the study of cancer) and limb regeneration, amon other topics, is:

      http://www.geron.com/

      The specific fram page with a discussion of their cancer research is:

      http://www.geron.com/03.01_oncology.html

      Intentional telomerase activation is generally only useful in wound healing therapies; this is because the cells in which the telomerase would act in this case have already specialized.

      It's not know whether or not telomerase could act on stem cells directly, permitting "farming" of stem cells (an interesting idea, raised by your question). My gut feeling on this would be "no", based on the existance of teratomas, but I'm willing to be wrong (particularly if it ends up making me immortal... 8-)). The regenerative medicine page is at:

      http://www.geron.com/03.03_regenmed.html

      Note that Geron (the company whose site this is) has the patent on the genes coding for human Telomerase, owns the patents that led to "Dolly the sheep", and is interesting for other reasons.

      The company was originally founded -- and their web page used to claim this -- to find a cure for human aging. They have a more mainstream message, these days, but they are certianly making progress on their original goal, even if they are getting a lot of products out of the intermediate work.

      -- Terry

  • A good read. (Score:3, Informative)

    by Anonymous Coward on Thursday September 26, 2002 @09:45AM (#4336253)
    The Body Electric by Robert O. Becker, MD. [amazon.com]

    This book describes the efforts of Becker to try to study human limb regeneration and how he was shot down at every opportunity by the establishment. A fine example of how university educated people turn into religious-style bigots.

    I didn't RTFA, but I'm sure it's a typical example of how Becker ridkes his career to bring to light new evidence, but 20 years later someone else takes the credit.

  • evolution? (Score:4, Insightful)

    by tid242 ( 540756 ) on Thursday September 26, 2002 @10:27AM (#4336623) Homepage
    Scientists wonder why the ability to regenerate has not spread more widely through evolution...

    ...the advanced immune systems of higher life forms may mistake rapidly proliferating cells for cancer and kill them.

    i find this a really interesting idea. Especially given that most cancers are not seen until after people are at an age where they generally have children (you've passed your genes on before you die of cancer). If you were to look at our pre-historic counterparts: if their life-expectancy were 20 years old and they had most of their offspring starting at 10-12 (these numbers are mostly guesswork on my part) then i would tend to think that evolutionally being able to regrow lost arms and legs would outweigh the ability to ward off cancer that doesn't strike until they're 25...

    This is much the same as the differences between the rates of Progeria and Huntington's disease in people (people with Progeria don't have kids, but people with Huntington's do as the onset isn't until their 40's) even though, they're (apparently) similiar genetic abnormalities (ie in population genetics not taking into accout inheritence, their incidences should be equal)...

    But getting back to regen/cancer: Of course there would be a fine balance between the two and figuring this out would involve lots of statistics and things my noggen doesn't compute so well, but i do find it interesting that there's so little regeneration in people.

    conversely to my first point, since most regeneration would have probably been selected for, to take place before child-bearing age, and as we've advanced culturally and civically (child-bearing age) has markedly increased, and it's doubtful that missing a leg destroys your chances of having offspring if you live with a family in a cottage as opposed to running through savannas away from man-eating beasts and the like, maybe all this makes sense... (did you understand my convoluded run-on sentence?).

    -tid242

    • oh yes, and would this theory then lead us to believe that our ancestors regenerated better than we do today?

      that was the original conclusion of my previous post, but somehow i forgot to include it! - damn the brain..

      -tid242

    • Especially given that most cancers are not seen until after people are at an age where they generally have children (you've passed your genes on before you die of cancer).

      I've know 2 kids that died of cancer. One of 'em had reached puberty, the other had not.

      I'm trying to to loose my cool because this being an emotional issue for me, I take offense at what you said.

      So, what I'm saying, is that your ideas are based on faulty data, and therefore your conclusions are equally flawed.

      And BTW, small children (up to around 3yrs old) can regenerate small bits (finget tips). Older kids cannot, and adult of course cannot. Yet the liver always regenerates...

      • Re:evolution? (Score:3, Informative)

        by tid242 ( 540756 )
        I've know 2 kids that died of cancer. One of 'em had reached puberty, the other had not.

        I'm trying to to loose my cool because this being an emotional issue for me, I take offense at what you said.

        i am a bit taken aback by this, what i said was by no means to insinuate that children do not develop cancer, nor surely to offend anyone. i think the key words here are "most cancers" this does not mean the same thing as all cancers. point of fact (US 2000 cancer stastics):

        incidence:
        male: Prostate (30% of all cancers), Lung (14%), Colon/rectum (11%), Bladder, Melanoma (5%), etc, etc, leukemia (3%),

        female: Breast, Lung, Colon, Uterine, etc. etc. (leukemia isn't even listed as one of the most common female cancers)

        cancer deaths:
        male: Lung(31%), Prostate (11%), Colon(10%), all others equal to or less than 5% (leukemia = 4%)

        female: Lung (25%), Breast(15%), Colon(11%), pancreaus (6%), all others less than 5% (leukemia = 4%)

        these stastics exclude non-melanoma skin cancers

        of cancers Leukemias (especially fast-growing leukemias such as ALL, which are amongst the most easily treated of all cancers, if this be any comfort for you) account for 30% of all childhood cancers (and i think neoplasms represent usually w/i the top 5 childhood killers, while the nation's non-age-adjusted 2nd largest killer only behind heart disease), leukemia is 10 times more common in adults than it is in children...

        all and all survival rates are higher in children than they are in adults, many times because of cancers specific to children, but also lending to a better chemotherapeutic/radiation tolerance in children allowing health-care providers to "push the dose..."

        while cancer does certainly present in children, the fact remains that children constitute a much smaller cancer population, (even when statistically adjusted for population-size).

        as i said before, it was not my intent to offend anyone, but the fact remains that general population trends show that cancer incidence increases with age (possible curtailing of the curve could be accounted for by genetic predispositions of cancer). Also, reember that personal experience is not necessarily indicitive of population trends. And likewise population trends does not necessarily reflect cancer incidence in your particular state, country, neighborhood, family, circle of friends, etc. So my original comment was not direct toward people you know, but toward the greater human condition. i am also painfully aware of the differences between statistics and the effect illnesses have had on my life and my family.

        my source [cancer.org] (american cancer society).

        -tid242

        • while cancer does certainly present in children, the fact remains that children constitute a much smaller cancer population, (even when statistically adjusted for population-size).

          Really? I thought it was because of the population size, or the fact that it takes a while to accumulate carcinogens.

          as i said before, it was not my intent to offend anyone

          Yeah, sorry about that...

          • NP (Score:1)

            by tid242 ( 540756 )
            Yeah, sorry about that...

            NP, i just feel bad when i make other people feel bad (innocent people anyway)..

            If you're interested here's a breakdown of causes of death by age provided by the CDC, it's actually pretty interesting... starting on page 13 or so: cdc.gov...pdf [cdc.gov] :)

            take care,

            -tid242

        • i am a bit taken aback by this, what i said was by no means to insinuate that children do not develop cancer, nor surely to offend anyone. i think the key words here are "most cancers" this does not mean the same thing as all cancers.
          Obviously, children do develop cancer to a certain defree. In an attempt to answer your question why evolution provided us with quite an amount of cancer protection, maybe it is because otherwise even children would develop much more cancer than they do now? Perhaps that would result in even less chance to reproduce than the gained advantage of regenerating lost body parts.
    • While it is correct that in today's aging population, the majority of cancers effect the elderly that did not exist over the course of evolution, cancer still affects the young. It makes more sense for the body to develop defense mechanisms guarding heavily against rapid, unchecked division of cells (apoptitic triggering proteins and the like), since you can still live and reproduce without a limb. Regeneration would also tax the body's resouces like little else could - liver regeneration and such are one thing, but the reformation of bone and tissue, including neural cells, would be extremely difficult for an adult. A child has the ability to sit and heal, and thusly can regenerate small damages. Basically, it just makes more sense physiologically to guard against cancer than the loss of a limb.
    • able to regrow lost arms and legs would outweigh the ability to ward off cancer that doesn't strike until they're 25...

      Perhaps the reason our ancestors did not develop cancer until after age 25 is because of the inherent mechanisms of prevention. Loss of these mechanisms would allow regeneration to be possible, but would increase the risk of death due to cancer at a younger age; say, 15 or 20. That would mean you'd die about the time your kids are 2 or 3. Of course, they would die shortly after.

      (did you understand my convoluded run-on sentence?).

      Maybe.... Loss of a leg and the subsequent regeneration would take, at the very least, several weeks, if not many months. This downtime would probably result in the person's death. Loss of a leg means no walking or running. Loss of an arm means you can't hunt or gather (not effectively, at least). That may reduce the selective advantage

      Another interesting note is that of the organisms that can regenerate on a large scale, I don't think any of them have a closed circulatory system. A closed circulatory system could introduce problems from a development standpoint (think about how a closed circ system is made in the embryo), and from the "oh-shit-where's-all-my-blood-going" standpoint.

    • That's sick.

      Pervert.

      Seriously though, that's below the age range where the average human is capable of reproducing. The other points are interesting, but that age guess is way out of wack.
  • Regeneration has been tried before,

    remember in spiderman? doctor with no arm uses techniques of regeneration only to backfire and he becomes a mean lizard man?!?

    i say leave well enough alone
  • Even if biomed engineers manage to create a way to regenerate natural limbs, would such a technique work for people born without legs [rose-hulman.edu]?
    • It seems to me that the main challenge in growing whole limbs would be the initial attachment of the new limb. Connecting nerves and tiny blood vessels is very difficult and fairly inexact as it is.

      Secondly, what about the nerves? You spend the first couple *years* of your life learning motor coordination and skills. I would imagine that it would be very very difficult for an adult to learn to use appendages he/she never had to begin with. We know that certain parts of the brain are more hardwired than others, and that rewiring can occur, but that, as well, is something we've only begun to dabble in.

      We still have a long way to go.

      J

  • And in a related story, Dr. Futzup, who works in a room adjacent to Dr. Ellen Heber-Katz, was feeding Nutrasweet to a group of mice for 3 weeks, and one morning when his lab assistant brought in the cage he noticed "three holes had appeared in all their ears!". Also, he noted "the cage had changed color!"
  • Have you ever gotten your ear peirced and didn't leave the ear ring in your ear long enough. It will grow over the hole filling the hole back in. If that is her only evidence that holes in mice ears are regenerating then I would have to say "Big Deal!"

    Now I guess what I might be missing is do mice ears regenerate like human ears or is it expected that the holes don't grow back?
    • or is it expected that the holes don't grow back?

      They normally don't grow back. The holes used in the ears of mice are an inventory mechanism. The holes are pretty big; the tool I use makes little semicircle notches about 1cm in diameter; quite a bit bigger than the holes in peirced ears for us.

      • "little semicircle notches about 1cm in diameter; quite a bit bigger than the holes in peirced ears for us"

        Ummm... have you been to a big city recently? The neo-tribal thing is "in" now, at least with a particularly degenerate crowd.

        Hopefully their inheritance will cover the price of a good plastic surgeon.

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