The Road to Regeneration
In the old days undergoing an amputation was like receiving a death sentence. Today, advancements in modern technology have made the amputation a fairly common procedure and some amputees even excel physically and perform better than they did before surgery. Engineers are forever creating lighter, faster, more efficient prosthetics for patients, but the amputee is never able to feel completely whole again. However, the regeneration of human limbs is on the horizon as scientists are learning to harness the natural ability of humans to re-grow their own tissue.
Our most in-depth understanding of the regeneration of limbs comes from a simple animal model – the salamander. When a salamander limb is initially amputated, blood vessels constrict and a layer of skin cells forms over the wound. Fibroblasts (cells that produce connective tissue) receive signals to migrate to the heart of the injury where they form the blastema. This blastema is the absolute key to regenerating a limb in a salamander because is serves as a site for the aggregation of progenitor cells. Fibroblasts, for example, can enter the blastema and transform into “undifferentiated” blastemal cells, from which point they can become skeletal tissues and then fibroblasts once again.
Humans are remarkably similar to salamanders with respect to regeneration of some tissues, including epidermis, interstitial connective tissue, adipose tissue, muscle, bone, and vasculature. All of these tissues have the capability to regenerate themselves after small scale injury. Still, there exists a large gap between the salamander and the human that we need to bridge. One of the biggest differences, for example, is that mammalian fibroblasts form scar tissue after injury while salamander fibroblasts do not. In both animals fibroblasts migrate to the wound, proliferate, and lay down a new extracellular matrix. However, mammalian fibroblasts proceed one step further by producing too much of the new extracellular matrix, which becomes abnormally cross-linked as the tissue ages. Thus the formation of scars is one of the greatest impedances to regenerating new limbs, along with the formation of a blastema where it would not normally occur.
Scientists have already created a blastema in a mouse where it would not normally exist. They hope to continue working with mice and transfer the work to humans in one or two decades. An exciting find by H. Chang and J. Rinn of Stanford shows that adult human fibroblasts do in fact contain a memory of their developmental stage, which could be utilized to help fibroblasts lay down a non-scarring matrix under proper conditions.
Muneoka K. et al. “Regrowing Human Limbs.” Scientific American. April 2008: 56-63.
Our most in-depth understanding of the regeneration of limbs comes from a simple animal model – the salamander. When a salamander limb is initially amputated, blood vessels constrict and a layer of skin cells forms over the wound. Fibroblasts (cells that produce connective tissue) receive signals to migrate to the heart of the injury where they form the blastema. This blastema is the absolute key to regenerating a limb in a salamander because is serves as a site for the aggregation of progenitor cells. Fibroblasts, for example, can enter the blastema and transform into “undifferentiated” blastemal cells, from which point they can become skeletal tissues and then fibroblasts once again.
Humans are remarkably similar to salamanders with respect to regeneration of some tissues, including epidermis, interstitial connective tissue, adipose tissue, muscle, bone, and vasculature. All of these tissues have the capability to regenerate themselves after small scale injury. Still, there exists a large gap between the salamander and the human that we need to bridge. One of the biggest differences, for example, is that mammalian fibroblasts form scar tissue after injury while salamander fibroblasts do not. In both animals fibroblasts migrate to the wound, proliferate, and lay down a new extracellular matrix. However, mammalian fibroblasts proceed one step further by producing too much of the new extracellular matrix, which becomes abnormally cross-linked as the tissue ages. Thus the formation of scars is one of the greatest impedances to regenerating new limbs, along with the formation of a blastema where it would not normally occur.
Scientists have already created a blastema in a mouse where it would not normally exist. They hope to continue working with mice and transfer the work to humans in one or two decades. An exciting find by H. Chang and J. Rinn of Stanford shows that adult human fibroblasts do in fact contain a memory of their developmental stage, which could be utilized to help fibroblasts lay down a non-scarring matrix under proper conditions.
Muneoka K. et al. “Regrowing Human Limbs.” Scientific American. April 2008: 56-63.
posted by Jackie Estes at 3:12 PM
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