Epimorphic Regeneration of Elastic Cartilage: Morphological Study into the Role of Cellular Senescence

SIMPLE SUMMARY: The complete regeneration of organs after damage is a distant future of regenerative medicine. One of the few rare mammal models of structural tissue restoration is the defect of the elastic cartilage plate in rabbit ear. Understanding why a complex tissue heals into itself and not into a scar brings us closer to controlling innate regenerative potential. In this experiment, we discovered that the regeneration of the elastic cartilage plate was associated with the presence of cells with the senescence-associated secretory phenotype (SASP). We investigated how the presence of these cells was defined by the defect size, and how they correlated with elastic fiber production and clinical outcome. It is possible that SASP cells regulate the structural reparation of the damaged tissue by paracrine signaling, making them a potential pharmaceutical target. ABSTRACT: Control over endogenous reparative mechanisms is the future of regenerative medicine. The rabbit ear defect is a rare model which allows the observation of the epimorphic regeneration of elastic cartilage. However, the mechanisms of phenotypical restoration of this highly differentiated tissue have not been studied. We modelled circular ear defects of different sizes (4, 6, and 8 mm in diameter) in 12 laboratory rabbits, and observed them during 30, 60, 90, and 120 day periods. Excised tissues were processed and analyzed by standard histological methods and special histochemical reactions for senescence associated-β-galactosidase and lectin markers. We demonstrated that larger defects caused significant elevation of senescence associated-β-galactosidase in chondrocytes. The fullness of epimorphic regeneration of elastic cartilage depended on the activation of cellular senescence and synthesis of elastic fibers. Further investigation into the role of cells with senescence-associated secretory phenotype in damaged tissues can present new targets for controlled tissue regeneration.