Gene-Based Retrodifferentiation Approach

In nature, one can find examples of both strategies to replace body parts (see Pearson, 2001). Within some invertebrates such as the cnidarian Hydra, populations of ‘totipotent’ stem cells are present throughout their lives. Upon transection, stem cells near the place of injury are mobilized and respond to local cues, regrowing the missing body part. In some vertebrates, such as amphibian urodeles, differentiated cells near the amputated plane can start proliferating and become dedifferentiated. These so-called blastemal cells produce a growing cone of cells that progressively redifferentiate into the original or other cell types needed to reconstruct the missing body part (reviewed in Brockes, 1997). This cellular plasticity is now the focus of intensive research aimed at identifying the similarities and differences allowing regeneration in these organisms and failing in humans. Recent studies mixing mouse and urodele skeletal muscle revealed that the mouse cells could be stimulated to reenter the cell cycle (McGann et al., 2001; Velloso et al., 2001). Efforts are now concentrating on identifying the factors that mediate the activation of proliferation in mammalian skeletal muscle.