Endothelial Effects in the Elderly: Fibroblast Regulation in Soft Tissue Healing

Abstract

Two main influencing factors of human soft tissue healing are concomitant diseases and cellular senescence, both accumulating with increasing age. Due to the raising population of the elderly in western countries, it is essential to enhance the level of knowledge concerning the function of senescence in a granulation tissue during repair. The present study was intended to verify classic markers of senescence, like senescence-associated ß-galactosidase and the development of a senescence-associated secretory phenotype among fibroblasts during emerging senescence. The application of an in vitro model using serial passaging as inducer of replicative senescence revealed specific differences of a non-senescent and a pre-senescent fibroblast phenotype in mono-cultures, representing the basis for a detailed examination of the phenotypes in their interaction with microvascular endothelial cells in co-cultures. The results deliver new insights into the age dependent process of tissue repair. Characteristics of pre-senescent fibroblasts in terms of modified proliferation, cell morphology, cell cycle regulation, myofibroblastoid differentiation and cytokine release indicate a strong responsibility of this phenotype for the composition and function of a granulation tissue at different locations, including vascular sites. In its entirety, the results support the assumption, that a missing clearance of the senescence phenotype in late stages of tissue repair is one of the main reasons for healing failure.