Abstract
Digit tip regeneration is one of the few examples of true multi-tissue regeneration in an adult mammal. The key step in this process is the formation of the blastema, a transient proliferating cell mass that generates the different cell types of the digit to replicate the original structure. Failure to form the blastema results in a lack of regeneration and has been postulated to be the reason why mammalian limbs cannot regrow following amputation. Understanding how the blastema forms and functions will help us to determine what is required for mammalian regeneration to occur and will provide insights into potential therapies for mammalian tissue regeneration and repair. This review summarizes the cellular and molecular mechanisms that influence murine blastema formation and govern digit tip regeneration.
Highlights
The ability of animals to regenerate lost body parts has fascinated scientists for centuries
When dermal fibroblasts were transplanted into a regenerative, but not non-regenerative digit, they were shown to acquire a blastema phenotype and contribute to bone regeneration [39]. These results indicate that cells within the mammalian digit tip blastema maintain some flexibility in terms of their fate and suggest that the local environment may, in part, specify the cell’s ultimate contribution to the regenerated tissue
This work has addressed the question of nerve dependency during mammalian digit tip regeneration and demonstrated that nerves contribute to regeneration through two complementary mechanisms: first, the provision of dedifferentiated Schwann cells that secrete growth factors into the local microenvironment; and second, through the contribution of nerve-derived mesenchymal cells that are able to differentiate into the regenerated mesenchymal tissues in response to local cues
Summary
The ability of animals to regenerate lost body parts has fascinated scientists for centuries. Among the handful of mammalian regeneration models, the mouse exemplifies an ideal system to study spontaneous regeneration, as the process of murine digit tip regeneration is akin to, and clinically relevant to, human fingertip regeneration Both digit tips are composed of skin, nerves, blood vessels, bones and tendons (figure 1), and regeneration requires all of these tissues to regrow in a temporally and spatially precise manner to replace the original structure and restore functionality. In both systems, digit tip regeneration is level dependent; injury following amputation of the distal region of the third phalangeal element regenerates, whereas amputations that occur more proximally, removing the nail bed, fail to regenerate [20,21,22,24,25,26]. If we can understand how the blastema forms and functions during digit tip regeneration this will provide clues as to how we can stimulate regeneration and repair of limbs and other tissues in mammals
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