Repair, Regeneration, and Differentiation in Humans

Although improvements in body armor have had a significant impact on reducing mortality in soldiers, ballistic damage to appendages such as arms and legs often results in loss of function or loss of the entire limb, leading to significant reductions in warfighter capability, and an increased medical logistics burden. At present, the ability to restore appendages or organ function in humans is marginal. However, the fact that many vertebrate organisms can regenerate developing limb buds and that humans can regenerate the tips of their fingers suggest that the genetic capacity for regeneration is present but "turned off" in adult humans. Consequently, a genetic and biochemical understanding of how regeneration occurs in an adult salamander could lead to insights as to how to "turn on" the latent regeneration cascade in humans, hence, leading to significant new therapies for battlefield wounds. This SBIR application proposes to address the general problem of tissue repair and regeneration in mammals by using the Urodele salamander's ability to grow an ectopic limb as an assay to rapidly screen different factors for regenerative activity. We believe that the development and use of this assay will eventually lead to the discovery and development of strategies for promoting the scarless healing of wounds and even the regeneration of severely damaged limbs.