Tuesday, April 17, 2012

Will we be able to regrow our limbs?

Wouldn’t it be great if humans could regenerate their limbs? If it were possible for humans to “regrow” their limbs, then amputees would have no more worries. In a short time, they would not appear to be amputees any longer. They would have their old lives back. Already, there are some animals that have this ability. Salamanders, for instance are known for their ability to regrow limbs. If we could somehow harness their ability to regenerate, the world of prosthetic limbs could be a thing of the past.

In order to begin to figure out how to make humans regenerate limbs, we have to first understand how organisms like salamanders do it. When a salamander loses a limb, a “tumorlike” group of cells called a blastema forms where the limb was removed (Humphries). In only three weeks, this group of cells can form a fully developed limb (ScienceDaily). It was originally thought that the blastema was composed of pluripotent cells (cells that can differentiate into any type), like stem cells. However, in 2009, a group of scientists discovered that this is not the case. Actually, the cells retain their original identities, muscle cells regenerate the muscles, bone cells regenerate the bones, etc. This greatly simplified the matter for scientists as it revealed that the presence of pluripotent cells was not necessary for limb regrowth. In fact, the regeneration of a limb is very similar to the healing of cuts or broken bones (Humphries).

However, this brought up the question: If salamander limb regeneration follows a similar mechanism to human wound repair, why can’t humans regenerate their limbs? Actually humans do have this ability in our earlier stages of development. Fetuses actually have the ability to regrow limbs, and young children can regrow fingertips. But why is this ability lost with adulthood? I found an interesting segment from show on the Science Channel that goes into more detail on the subject.

In case you don’t feel like watching it, basically, it has to do with the extracellular matrix. The extracellular matrix is what carries information to the cells to effectively tell them what they should be doing: growing, moving somewhere else, differentiating, etc. In salamanders, the nature of the blastema allows the extracellular matrix to keep contact with the cells on the outermost of the wound. In humans, we don’t have this blastema, so the extracellular matrix is cut off from the outermost part of the wound, preventing the message of regeneration from getting to the outermost cells. This problem was solved by a scientist who decided to try isolating the extracellular matrix from pig bladders and applying it to the site of his brother’s severed finger. Lo and behold, the fingertip was able to regenerate in a few weeks, fingernail and all, a feat that was previously unheard of in older men. This scientist is particularly optimistic regarding the possibility of extending this to include the regeneration of an entire hand.

Finger regeneration before and after from the above video
Now, here comes the evolutionary biologist’s question: why would a salamander maintain contact with between its wounds and extracellular matrix while we don’t? What evolutionary process led to that difference? Well, the only explanation I could specifically find was that because salamanders are amphibians, their cells need to retain flexibility for metamorphosing (“Why can’t we…?”). However, I wasn’t satisfied with this explanation because while this explanation addresses why juvenile salamanders retain fetus-like flexibility, it does not fully explain why adult salamanders do not lose this ability just as adult humans do. So, I was thinking about it and I think I came up with a possible explanation. Because amphibians have evolved to be both aquatic and terrestrial animals, their skin has evolved in a different way than human skin. Amphibians must make sure to have their skin constantly moist while human skin is dry most of the time. Perhaps it is this necessity that fostered the development of a way to keep the cells always surrounded by the extracellular matrix. This is of course just my own speculation, so if you have another explanation that better explains it, please let me know!

Fortunately, we have made great strides in the study of regeneration technologies in the past few years. Hopefully, it won’t be long before we’ll only see prosthetics in the history books.    

Humphries, Courtney. “A Limb Regeneration Mystery Solved” 2009. http://www.technologyreview.com/biomedicine/22955/page1/

Science Daily. “Salamanders, Regenerative Wonders” 2009. http://www.sciencedaily.com/releases/2009/07/090701131314.htm

“Why can’t we regenerate limbs like other species?” 1999. http://www.straightdope.com/columns/read/1660/why-cant-we-regenerate-limbs-like-other-species


  1. Wow, such a cool article. So to clarify, the extracellular matrix derived from the pig bladder and applied to the end of the damaged finger was then able to carry on connection and regeneration coordinated by the extracellular matrix on the other side of the injury?

  2. It is a really cool article. I am just wondering what's the role of extracellular matrix in the development of cancer cells? Is there any way for scientists to prevent the signal transfer between cancer cells...It seems an inverse technique compared to above problem.---Yang Zhang

  3. Estevan, that's my understanding of it from what I saw in the video. All we have to do is let the body connect with its regenerative power. Also, something I just noticed when looking back at the picture I posted, it appears that it was even able to regenerate the fingerprint! Pretty crazy stuff.

    Yang, that's an interesting point! I just looked it up and I found an article saying that extracellular matrix proteins do increase the ability of lung cancer cells to form tumors. http://www.ncbi.nlm.nih.gov/pubmed/10371505

    Only thing about the treatment idea is that I'm unsure of how to prevent transfer between cancer cells without also depriving healthy cells of the extracellular matrix. That's definitely something that's worth researching, though!

  4. From what I can tell, the ability to regenerate full limbs in vertebrae is mostly limited to newts and salamanders, although I know that there are certain species of lizards that can regenerate their tails, which is about as biologically complex as reforming a limb. The extracellular matrix experiment shows that this functionality is still present in mammals, just localized to smaller sections of the body. Maybe there's a greater cost to mammals to regenerating limbs in the way of increased tumor formation, and to avoid this, natural selection localized the regeneration process to tissue and not to higher structures. Good read!

    1. That's a good point. I hadn't thought about the evolutionary advantage of avoiding the development of harmful tumors. However, how would it be any different for salamanders and newts? Wouldn't they have an equal likelihood of developing harmful tumors? Wouldn't they need to avoid forming them as well? On the contrary, they form a benign (or actually helpful) tumor for the specific purpose of regeneration. What is the instance of cancerous growths in those animals, I wonder? Definitely something interesting to think about. Thanks!

  5. So starfish and salamanders have this ability. How about amniotes? Do any of them have this ability? Could this have had something to do with the split between amniotes and amphibians, where the development of the fetus changed to grow on land? My theory is that in order to have a fetus grow on land, some things were given up, since there are only a limited amount of resources in the egg. Potentially, this ability to regenerate (i.e. produce extracellular matrix) was lost in transition in order to have terrestrial eggs. Why the regeneration capability might've been lost simultaneously, I've no idea. I can think of a few other things I would've rather lost.

    1. That's a good question! I hadn't thought of that possibility. I actually just looked it up and yes, there are lizards that regenerate their tails using a blastema, just as salamanders and newts do. Here's the link to the paper if you want to look at it. http://sphotos.xx.fbcdn.net/hphotos-snc7/312570_10150519885243858_653343857_11649017_2065976072_n.jpg

      However, it is a pretty specified process. Having this specialization for the regrowth of a tail has obvious benefits in allowing lizards a way to escape predators. Perhaps the ability to form a blastema and regenerate phased out in that way where first it was reduced to only applying to the tail, and then when it was not as useful for other species to escape predators by losing their tails, it lost the tail regeneration too.

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