Can People Regenerate Body Parts? (II of V)

Scientific American Magazine - By Ken Muneoka, Manjong Han and David M. Gardiner

Many years ago studies in the laboratory of our colleague Susan V. Bryant at the University of California, Irvine, demonstrated that the cells in the blastema are equivalent to the cells in the developing limb bud of the salamander embryo.

This discovery suggested that the construction of a limb by the blastema is essentially a recapitulation of the limb formation that took place during the animal’s original development. An important implication of this insight was that the same genetic program is involved in both situations, and because humans make limbs as embryos, in principle we should already have the necessary programming to regenerate them as adults, too. It seemed, therefore, that all scientists needed to do was figure out how to induce an amputated limb to form a blastema.

One of us (Gardiner)—working with Tetsuya Endo of U.C. Irvine a few years ago—took a minimalist approach to answering the basic question of how to make a blastema. Instead of studying amputation sites on the salamander, where a blastema would naturally form, we looked at simple wounds on the side of a salamander limb, which would normally heal just by regenerating the skin. Our idea was that such wounds are similar to the site of an amputated mammalian limb that fails to generate a new limb. If we could get an entire limb to grow where a simple wound-healing response would typically occur, then we could further dissect the regeneration process.

After we made a small incision in the salamander leg, epidermal cells migrated to cover and seal the wound, as they would at an amputation site, and fibroblasts from the dermis layer of the skin also moved in to replace the missing skin. But if we carefully deviated a nerve to the wound site, we could induce those fibroblasts to form a blastema instead. Marcus Singer of Case Western Reserve University had already demonstrated more than half a century ago that innervation was required for a regeneration response, but our experiments clarified that unknown factors provided by the nerve were influencing regeneration by altering the behavior of resident fibroblasts. These induced blastemas never progressed to the later stages of regeneration to form a new limb, however. One more ingredient was needed.

The key to inducing a blastema that produced a new limb was to graft a piece of skin from the opposite side of the limb to the wound site, which allowed fibroblasts from opposite regions of the limb to participate in the healing response. The resulting accessory limb was, of course, growing out at an abnormal location, but it was anatomically normal. So the basic recipe for making a blastema seemed relatively simple: you need a wound epidermis, nerves and fibroblasts from opposite sides of the limb.

With this minimal view of limb regeneration in mind, we began to focus on understanding the roles of the individual ingredients.

info@goliveideas4.com >> http://www.goliveideas4.com