Study of Natural Longlife Juvenility and Tissue Regeneration in Caudate Amphibians and Potential Application of Resulting Data in Biomedicine

Abstract

The review considers the molecular, cellular, organismal, and ontogenetic properties of Urodela that exhibit the highest regenerative abilities among tetrapods. The genome specifics and the expression of genes associated with cell plasticity are analyzed. The simplification of tissue structure is shown using the examples of the sensory retina and brain in mature Urodela. Cells of these and some other tissues are ready to initiate proliferation and manifest the plasticity of their phenotype as well as the correct integration into the pre-existing or de novo forming tissue structure. Without excluding other factors that determine regeneration, the pedomorphosis and juvenile properties, identified on different levels of Urodele amphibians, are assumed to be the main explanation for their high regenerative abilities. These properties, being fundamental for tissue regeneration, have been lost by amniotes. Experiments aimed at mammalian cell rejuvenation currently use various approaches. They include, in particular, methods that use secretomes from regenerating tissues of caudate amphibians and fish for inducing regenerative responses of cells. Such an approach, along with those developed on the basis of knowledge about the molecular and genetic nature and age dependence of regeneration, may become one more step in the development of regenerative medicine

Tail and Spinal Cord Regeneration in Urodelean Amphibians

“…In salamanders, pedomorphosis has been identified in both forms and has been shown to be regulated by a thyroid hormone (TH) in both cases [57][58][59]. The existing explanations for the high regenerative capacity in salamanders are associated with pedomorphosis as a key ontogenetic factor permissive to regeneration [9,60]. It is also known that pedomorphosis correlates with an increase in genome size, which, in turn, positively correlates with cell size but negatively correlates with the rate of cell proliferation and differentiation [61].…”

Self-Organization of the Retina during Eye Development, Retinal Regeneration In Vivo, and in Retinal 3D Organoids In Vitro

“…In this case, it is possible to assume some similarity of extrinsic signaling factors acting in the development and in the adult state in newts. This assumption is based on the fact of the paedomorphic status of newts, which retain a number of juvenile traits upon reaching maturity [ 158 , 159 , 160 ].…”

“…This capability is important, since non-hereditary retinal damages occur more frequently in an adult organism and should be subject to correction also in it. The advantages of these models also consist of the good knowledge of the phenomenon, the knowledge of the genomes of model newt and frog species, the low rate of the regeneration process (over 1 month), and large cell sizes with their smaller number in the populations of specific NR cell types [ 160 ].…”

Pigment Epithelia of the Eye: Cell-Type Conversion in Regeneration and Disease

“…Recently, in a study of changes in the epigenetic landscape in mouse RPE cells, an assumption has been made that the expression of “pioneer” TFs in amphibians, as well as the demethylation of regulatory elements of photoreceptor genes, is possible in the RPE cell-type conversion [ 165 ]. It is likely that, in sexually mature, paedomorphic newts that initially have juvenile properties [ 166 ], the reduction in the level of differentiation (necessary for the conversion) with the involvement of signal–response enhancers, including epigenetic ones, does not require large-scale modifications of gene expression.…”