American military armor is better designed than ever before to protect soldiers on the battlefield from being killed. While that has drastically lowered the number of U.S. soldier casualties in the wars in Iraq and Afghanistan, thousands of soldiers are returning stateside with serious burns, missing limbs and other debilitating injuries. To improve treatment options for the veterans, the Pentagon recently announced its plan to devote $250 million to research on regenerating human skin, ears and muscles for injured soldiers [source: Reuters]. Part of that funding will also establish the Armed Forces Institute of Regenerative Medicine that will focus on human limb regeneration, among other things.
Limb regeneration doesn't mean growing arms and legs in test tubes; instead, it means that a person would actually regrow a limb. Scientific evidence indicates that humans have the potential for limb regeneration in our genes, but those genes are dormant in our bodies [source: Kotulak]. Human embryos, for instance, can regrow limb buds in the womb [source: Muneoka, Han and Gardiner]. And a man in Cincinnati, Ohio, regrew a fingertip after accidentally slicing it off in 2005. But when you lose an entire limb, the body reacts by covering that wound site with thick scar tissue to ward against infection.
To figure out how we might be able to reignite that genetic potential for limb regeneration, researchers are starting small -- with mice. But they aren't having to work entirely from scratch to track down how an organism could regrow something. They're looking to the salamander as their model.
Salamanders are part of the amphibian family, members of which are cold-blooded and have an additional skin covering of feathers or fur. Different species of salamanders are either terrestrial or aquatic and are the only amphibians with tails. In case they lose that precious tail, salamanders can grow it back. They're the highest order of animals capable of regenerating body parts, including their tails, upper and lower jaws, eyes and hearts.
How does this relatively simple creature perform a science-fiction style anatomical magic trick?
Salamander Limb Regeneration
If a salamander gets in a fight, it may surrender its tail to the enemy as a defense mechanism. After all, in a few weeks time, it can grow a new one. This is a pretty complex process, but in a nutshell, regeneration involves shuffling around the cells at the wound site and assigning them a new specialization.
Within in the first hours after getting a body part lobbed off, the salamander's epidermal cells in the area migrate to cover the open flesh. That layer of cells gradually thickens in the following days, forming the apical epithelial cap [source: Muneoka, Han and Gardiner]. Cells within the salamander's tissues called fibroblasts also congregate beneath that epidermal covering. Fibroblasts are undifferentiated, which means that they're free to become multiple types of cells, depending on which body part needs replacing.
After that initial phase, the blastema develops from the mass of fibroblasts; the blastema will eventually become the replacement body part. Researchers recently discovered that the expression of a protein called nAG kick-starts blastema growth [source: Kumar et al]. The blastema is sort of like a mass of human stem cells in that it has the potential to grow into various limbs, organs and tissues. But how does the salamander's body know what needs replacing? The genetic coding in the blastema contains a positional memory about the location and type of missing body part. That data is stored in the Hox genes in the fibroblast cells [source: Muneoka, Han and Gardiner].
While this is happening, capillaries and blood vessels are regenerating into the blastema. As the blastema cells divide and multiply, the resulting mass becomes a bud of undifferentiated cells. In order for that mound to become a full-fledged limb, tail or other body part, it must receive stimulation from nerves [source: Kumar et al]. However, when salamanders drop their tails, they lose not only flesh but also nerves. That means that nerve axon regeneration is happening at the wound site in tandem with tissue, bone and muscle regeneration.
From there, the cells differentiate and create the appropriate body part. As part of that positional memory in the fibroblast cells, the blastema knows to grow in the proper sequence to avoid defective regeneration. For example, if a salamander loses a foot at its ankle, the blastema will develop outward to form a foot instead of an entire leg.
With the salamander as the blueprint, scientists hope to someday engineer blastemas from human cells. Until then, our amphibian friends are still the reigning regenerators of the animal kingdom.
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More Great Links
- Brockes, Jeremy P. and Kumar, Anoop. "Appendage Regeneration in Adult Vertebrates and Implications for Regenerative Medicine." Science Magazine. Dec. 23, 2005. (Oct. 28, 2008)http://www.sciencemag.org/cgi/content/full/310/5756/1919
- Bryner, Jeanna. "How Salamanders Sprout New Limbs." LiveScience. Nov. 1, 2007. (Oct. 28, 2008)http://www.livescience.com/animals/071101-newt-limbs.html
- Kotulak, Ronald. "Research brings hop body parts can regrow." Knight Ridder Tribune Business News. Sept. 29, 2006.
- Kumar, Anoop et al. "Molecular Basis for the Nerve Dependence of Limb Regeneration in an Adult Vertebrate." Science Magazine. Nov. 2, 2007. (Oct. 28, 2008)http://www.sciencemag.org/cgi/content/full/318/5851/772/DC2
- Muneoka, Ken; Han, Manjong; and Garinder, David M. "Regrowing Human Limbs." Scientific American. April 2008. (Oct. 28, 2008)http://www.sciam.com/article.cfm?id=regrowing-human-limbs
- Philipkoski, Kristen. "Grow Your Own Limbs." Wired Magazine. Sept. 22, 2006. (Oct. 28, 2008)http://www.wired.com/medtech/genetics/news/2006/09/71817?currentPage=1
- Ritter, Malcolm. "Regrowing of Fingers Gets Set for Trial Stage." St. Louis Post-Dispatch. Feb. 19, 2007.
- Stocum, David L. "Regenerative Biology and Medicine." Academic Press. 2006. (Oct. 28, 2008)http://books.google.com/books?id=3Ue5oF3INKsC
- Tsonis, Panagiotis. "Limb Regeneration." Cambridge University Press. 1996. (Oct. 28, 2008)http://books.google.com/books?id=hYwPxRg0EEkC