Human senescent fibroblasts trigger progressive lung fibrosis in mice
Fernanda Hernández‐González, Neus Prats, Valentina Ramponi, José A López-Domínguez, Kathleen Meyer, Mònica Aguilera, María Isabel Muñoz Martín, Daniel Martı́nez, Àlvar Agustí, Rosa Faner, Jacobo Sellarés, Federico Pietrocola, Manuel Serrano
Abstract
when delivered into the lungs of mice, whereas the conditioned medium (CM) from non-senescent fibroblasts lacks these activities; and, (3) navitoclax, nintedanib and pirfenidone ameliorate lung fibrosis induced by senescent human fibroblasts in mice, albeit only navitoclax displayed senolytic activity. We conclude that human senescent fibroblasts, through their bioactive secretome, trigger a progressive fibrogenic reaction in the lungs of immunodeficient mice that includes the induction of paracrine senescence in the cells of the host, supporting the concept that senescent cells actively contribute to disease progression in patients with f-ILDs.