Cellular plasticity in vertebrate regeneration

Abstract

Within the animal kingdom, there are several examples of organisms with remarkable regenerative abilities. Among vertebrates, newts appear to be the most adept at replacing lost structures and injured organs and can regenerate their limbs, tails, spinal cords, jaws, retinas, lenses, optic nerves, intestines, and heart ventricles. This regenerative ability is dependent on the induction of an unusual degree of cellular plasticity near the site of injury. Mature cells lose their differentiated characteristics and revert to proliferating progenitor cells that will later redifferentiate to replace the lost or injured tissues. This degree of cellular plasticity appears to be restricted to those vertebrates with the most remarkable regenerative abilities and is not observed in mammals. However, in the last several years, there have been a few studies suggesting that certain factors present in newt tissues can induce a dedifferentiation response in mammalian cells. These results suggest that the knowledge gained from studying the molecular basis of cellular plasticity in newts and other regeneration-competent model organisms might one day be used to enhance the regenerative potential in mammals.

Dedifferentiation and the role of sall4 in reprogramming and patterning during amphibian limb regeneration

“…The mechanisms that allow dedifferentiation after tissue injury and the plasticity or reprogramming potential of dedifferentiated limb cells are of key importance in the field of vertebrate regeneration and recent work in this field has been reviewed by several investigators (Brockes and Kumar, 2002;Odelberg, 2005;Straube and Tanaka, 2006;Stocum and Zupanc, 2008;Tsonis, 2008;Christen et al, 2010;Tamura et al, 2010). The present review addresses two questions about dedifferentiation in regenerating amphibian limbs, which are discussed in light of new studies in other models of regeneration or cell reprogramming.…”

Blastema cells derived from New Zealand white rabbit’s pinna carry stemness properties as shown by differentiation into insulin producing, neural, and osteogenic lineages representing three embryonic germ layers

“…Nevertheless, ASCs have a lower differentiation capacity, which limits their efficacy for clinical applications (Poulsom et al 2002;Patel and Genovese 2011). These drawbacks have motivated scientists to look for cells involved in the regenerative phenomenon, which is a sequential set of cellular processes including dedifferentiation, migration, proliferation, and finally redifferentiation of cells close to the site of injury (Odelberg 2005;Carlson 2007). Cellular dedifferentiation is a unique process in which fully differentiated cells revert to proliferating progenitor cells that, in some cases, leads to the formation of a blastema tissue (Tsonis 2000;Brockes and Kumar 2002;Odelberg 2004;Stocum 2012).…”

“…Therefore, blastema tissue contains undifferentiated and proliferating cells that are able to redifferentiate to specific cell types as required (Lemischka 1999;Carlson 2007). These processes, cellular dedifferentiation and blastema formation, are especially prominent in some animals with regenerative abilities, such as hydra (Galliot et al 2006;Bosch 2007a, b), planarians (Reddien and Sánchez Alvarado 2004), zebrafish (Poss et al 2003;Poss 2007), salamanders, axolotls and newts (Odelberg 2005;Brockes and Kumar 2005). There are also several reports on limited regeneration in mammals, including the regrowth of fingertips in mouse (Han et al 2008), antlers in deer (Li et al 2014), and ear hole closure in rabbit (Goss and Grimes 1975).…”

miRNA Control of Tissue Repair and Regeneration

“…17 The sources of such cell populations are limited. In response to a strong microenvironmental cue triggered by the injury, behavior of some of the cells in close proximity of the injury site changes to accommodate the emergence of new cell types.…”