Regeneration of Vertebrate Tissues: Model Systems

Abstract

Vertebrate animals exhibit four mechanisms of tissue regeneration: re‐growth of cellular parts, such as nerve axons; lineage‐specific proliferation of differentiated cells with or without dedifferentiation; transdifferentiation and activation of adult stem cells. The most common mechanism is the proliferation and differentiation of adult stem cells, used by epithelia, muscle, bone and blood. In some cases, such as the liver and pancreas, regeneration is accomplished by either lineage‐specific proliferation of differentiated cells or a stem cell population, depending on the nature of the damage. All four mechanisms are used by urodele salamanders in the regeneration of limbs. The cellular activities in all these mechanisms are regulated by a wide variety of growth factor signalling pathways and transcription factors. Regenerative medicine uses three major strategies based on knowledge of regenerative mechanisms: transplants of stem cells or their derivatives, construction of bioartificial tissues composed of natural or synthetic biomaterials seeded with cells and the pharmaceutical induction of regeneration at the site of injury by natural or synthetic regeneration‐promoting molecules. Key Concepts Regeneration restores the original structure and function of damaged or missing tissues. Tissues use four mechanisms to regenerate: re‐growth of cell parts, lineage‐specific reproduction of parent cells, transdifferentiation and activation of adult stem cells. Some tissues use more than one mechanism of regeneration. Growth factor signals and transcription factors are important regulators of regeneration. Regenerative medicine uses three strategies to regenerate damaged tissues: cell transplants, bioartificial tissue implants and pharmaceutical induction of regeneration directly at the site of damage by scaffolds or soluble molecules. The source of cells for transplants and bioartificial tissues is a crucial issue for regenerative medicine. Induced pluripotent stem cells (iPSCs) and/or transdifferentiation may solve many of the problems presented by adult and embryonic stem cells.