Regeneration - The Road Not Taken

Regeneration and repair are mutually-exclusive, adaptive responses to injury. The events associated with each process are well characterized. However, cellular and molecular mechanisms for their regulation are only now beginning to be defined. Moreover, full appreciation for factors that predispose to these contrasting pathways is not yet available. This article presents a perspective on regeneration and repair that suggests specific relationships between these modes of responding to injury. Injury provokes a coordinated pattern of response to tissue damage. At the wound site, local events determine whether tissue restoration or replacement occurs. Interplay among parenchymal and stromal cells at the site of injury, elements of the inflammatory infiltrate, and components of the immediate wound environment contribute to selecting an effector population for activation. The proposed model suggests that selecting parenchymal cells over stroma favors regeneration while the opposite favors repair. In addition, this model indicates that an integral aspect of both processes is the reintegration of effector cells into the damaged tissue or organ. Numerous illustrations suggest that regeneration and repair share common roots but diverge after injury. Viewing regeneration and repair as two equivalent pathways along the same continuum provides an integrative approach to resolving the apparent contrasts between these two means of responding to injury. Focusing on their parallels should facilitate defining means through which crossover from one process to the other might be achieved