| Summary: | In tissues characterized by a high turnover or following acute injury, regeneration replaces damaged cells and is
involved in adaptation to external cues, leading to homeostasis of many tissues during adult life. An understanding
of the mechanics underlying tissue regeneration is highly relevant to regenerative medicine-based interventions. In
order to investigate the existence a leitmotif of tissue regeneration, we compared the cellular aspects of
regeneration of skin, nerve and skeletal muscle, three organs characterized by different types of anatomical and
functional organization. Epidermis is a stratified squamous epithelium that migrates from the edge of the wound
on the underlying dermis to rebuild lost tissue. Peripheral neurons are elongated cells whose neurites are organized
in bundles, within an endoneurium of connective tissue; they either die upon injury or undergo remodeling and
axon regrowth. Skeletal muscle is characterized by elongated syncytial cells, i.e. muscle fibers, that can temporarily
survive in broken pieces; satellite cells residing along the fibers form new fibers, which ultimately fuse with the old
ones as well as with each other to restore the previous organization. Satellite cell asymmetrical division grants a
reservoir of undifferentiated cells, while other stem cell populations of muscle and non-muscle origin participate in
muscle renewal. Following damage, all the tissues analyzed here go through three phases: inflammation,
regeneration and maturation. Another common feature is the occurrence of cellular de-differentiation and/or
differentiation events, including gene transcription, which are typical of embryonic development. Nonetheless,
various strategies are used by different tissues to replace their lost parts. The epidermis regenerates ex novo,
whereas neurons restore their missing parts; muscle fibers use a mixed strategy, based on the regrowth of missing
parts through reconstruction by means of newborn fibers. The choice of either strategy is influenced by the
anatomical, physical and chemical features of the cells as well as by the extracellular matrix typical of a given tissue,
which points to the existence of differential, evolutionary-based mechanisms for specific tissue regeneration. The
shared, ordered sequence of steps that characterize the regeneration processes examined suggests it may be
possible to model this extremely important phenomenon to reproduce multicellular organisms.
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