Human Amnion Epithelial Cells Repair Established Lung Injury

Abstract

With a view to developing a cell therapy for chronic lung disease, human amnion epithelial cells (hAECs) have been shown to prevent acute lung injury. Whether they can repair established lung disease is unknown. We aimed to assess whether hAECs can repair existing lung damage induced in mice by bleomycin and whether the timing of cell administration influences reparative efficacy. In addition, we aimed to characterize the effect of hAECs on fibroblast proliferation and activation, investigating possible mechanisms of reparative action. hAECs were administered intraperitoneally (IP) either 7 or 14 days after bleomycin exposure. Lungs were assessed 7 days after hAEC administration. Bleomycin significantly reduced body weight and induced pulmonary inflammation and fibrosis at 14 and 21 days. Delivery of hAECs 7 days after bleomycin had no effect on lung injury, whereas delivery of hAECs 14 days after bleomycin normalized lung tissue density, collagen content, and α-SMA production, in association with a reduction in pulmonary leucocytes and lung expression of TGF-β, PDGF-α, and PDGF-β. In vitro, hAECs reduced proliferation and activation of primary mouse lung fibroblasts. Our findings suggest that the timing of hAEC administration in the course of lung disease may impact on the ability of hAECs to repair lung injury.