The role of senescence in regeneration

We want to learn from the nature of the senescence phenotype to take therapeutic advantage of those parts which are positive for (bone) regeneration, but overcome the disadvantages compromising new tissue formation.

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Senescence is an irreversible cell cycle arrest linked to tumor suppression and aging. In contrast, developmental senescence is a programmed and instructive process, which shares common signatures of stress-induced senescence. Since bone healing is thought to be the repetition of bone neogenesis, it may also depend upon the temporally and spatially regulation of cellular senescence. However, the exact role of senescence in regeneration and the impact of age and the mechanical environment still

ASC (Adult Stem Cell) aging is characterized by a reduced response to environmental stimuli, which leads to increased cellular senescence and a progressive decline in regenerative capacity. However, recent evidence implies that cellular senescence can also play a positive role in tissue regeneration, possibly due to paracrine signaling. The interplay between mechanical stimulation and senescence of ASCs during bone regeneration is still poorly understood. Using 3D bioreactors, we currently investigate the intracellular signaling response to mechanical stimuli of young and aged human MSCs (Mesenchymal Stromal Cells) and analyze their secretion pattern. Concurrently, we explore the interaction of mechanical stimulation and cellular senescence and its relevance for fracture healing in vivo using mouse models with reduced and enhanced cellular senescence.