Regeneration and the underlying mechanisms.

Abstract

Regeneration is generally defined as tissue replacement after pathological insult such as injury or disease. It has captured the attention of many biologists, clinicians and biomedical engineers, because understanding how regeneration is regulated will accelerate the development of regenerative medicine. Although many animals, including mammals, are able to regenerate damaged tissues, the degree to which this is possible varies considerably among species, as well as among their different body parts and tissues/organs. Consequently, various model organisms and systems, each offering specific strengths and weaknesses, are used to study regeneration in all its complexity. At the cellular level, the regenerative strategies, for example the source of cells regenerating a structure, are shown to differ widely between species and systems. In contrast, the molecular regulation seems less variable, as the same signaling pathways are commonly found to play crucial roles. The most important are Transforming growth factor β (TGF β), Fibroblast growth factor (FGF) and Wnt/β-Catenin signaling, directing all stages of the regenerative process across species and structures. Further, signaling through the growth factors IGF, VEGF, EGF and HGF, as well as MEIS- and Homeobox-factors is repeatedly found to be required for successful regeneration. Moreover, experimental interference with specific signals was shown to have the power to augment or even trigger the regenerative process in certain contexts, which allowed increasing our understanding of how regeneration is regulated. Here, I will give an overview of the different cellular aspects of regeneration and discuss the underlying molecular regulations. Differences and similarities between species and structures will be put forward and will furthermore be set into an evolutionary context. In addition, important future directions for regeneration research will be pointed out.