The regeneration of a mouse tail
Amphibians can regrow lost limbs, and lizards grow a new tail when the old one is severed. In mammals, however, injured tissue only heals, but severed pieces are not regenerated in a fully differentiated form. However, a particular strain of mice is in able to reproduce tissue correctly. This exception among mammals represents a unique strain of mice described by Ellen Heber-Katz of the Wistar Institute in Philadelphia at the February 1998 annual meeting of the American Association for the Advancement of Science. The mice offer hope that one day we will be able to induce at least some degree of tissue regeneration in humans.
Heber-Katz described how her research team discovered the regenerative ability of the mouse strain more by accident. To identify individual experimental mice, small patterns of holes were pricked in their ears. These holes do not usually heal and thus provide a permanent marking pattern. This time, however, the holes in the ears were completely closed after three weeks.
At first, researchers thought they had discovered a strain with exceptional wound-healing properties. Upon closer inspection, however, they noticed that there was no scar tissue at all-the hole was filled with fully differentiated epidermis, skin, and cartilage. With normal healing, a protein matrix forms over the wound, which then creates the scar. In these mice, the matrix had collapsed and been replaced by differentiated tissue. Heber-Katz realized that this was more of an amphibious regeneration than a cure.
Of course, the researchers couldn't just remove the mice's legs to see if limbs would grow back; however, they tested what would happen if the tip of the tail were clipped. After about an inch of the tail was severed, the tip grew back to about three quarters of the original length. The tissue regenerated perfectly - even the fur grew back. Liver tissue in these mice was also regenerated to achieve the correct mass. Liver tissue does grow back in normal animals, but growth is slower and tends to overgrow the correct mass and then slowly shrink back to normal size.
If the mouse tail was injured more severely, only the amount of bleeding prevented it from growing back successfully. When the wound had to be cauterized or tied off, it healed just like normal mice with scars. Heber-Katz suspected that this might be the biggest obstacle standing in the way of regeneration in humans.
Normal mammals appear to have traded the ability to regenerate tissues for a sophisticated immune system that actively prevents the new tissue from growing, thus serving as protection against tumor formation. Heber-Katz draws parallels between the mice and an embryo's ability to heal without scarring: 'Fetal wound healing is scarless and occurs before the development of the immune system's T cells.' The regenerating mice possess an unusual immune system and may lack a certain population of T cells, at least later in life. The researchers have identified seven unusual chromosomal sites and a potential gene that controls the response. However, the mechanism involved is still a mystery.
Heber-Katz believes that one day we may be able to activate genes at the site of injury. This would "ultimately make it possible to support organ replacement, as well as improve healing of chronic wounds, burns and spinal cord injuries," although there are many hurdles to overcome even to avoid scarring.
The idea of growing a new limb complete with bone, muscle, functioning nerves and perfect skin still belongs in the realm of science fiction.
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