The secretome of induced pluripotent stem cells (iPSC) modulates macrophage phenotype in the fibrotic lung

Abstract

Background: Macrophages are involved in the pathogenesis and progression of pulmonary fibrosis (PF). Imbalance between M1 and M2 macrophages could play role in progression of PF. The secretome from human induced pluripotent stem cells (iPS) reduce bleomycin induced fibrosis in the rat lung. We investigate the effect of iPS conditioned media (iPS-cm) on macrophages. Methods: Human monocytes were polarized towards M1 and M2 phenotype, and treated with iPS-cm; migration and secretory properties were tested in vitro . Bleomycin injured rats were treated on d7 either with iPSC-cm or CCD1-cm; FACS analysis was performed on d14. Results: iPS-cm increased migration of macrophages in vitro . Levels of proinflammatory and profibrotic mediators were reduced after in vitro treatment with iPSC-cm. In vivo , percentage of total macrophages increased in bleomycin injured lungs compared to control. Moreover, M1 and M2 populations were both increased in bleomycin group. Interestingly, iPS-cm treatment reduced total percentage of macrophage; moreover, the original macrophage phenotype was partially restored. These effects couldn9t be detected using CCD1-cm. Conclusions: iPS-cm modulates migration and alters the macrophage phenotype by reducing pro inflammatory and pro fibrotic mediators in vitro and alters macrophage percentage and phenotype in vivo in a lung injury and fibrosis model. Targeting the macrophage phenotypical switch could be a possible therapy for PF.