The Ritchie Centre, Monash Institute of Medical Research, Monash University, Clayton, Victoria, Australia.
Cell Transplant. 2013;22(8):1337-49. doi: 10.3727/096368912X657657. Epub 2012 Oct 4.
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.
为了开发用于慢性肺部疾病的细胞疗法，已经证明人羊膜上皮细胞（hAEC）可以预防急性肺损伤。但是否可以修复已建立的肺部疾病尚不清楚。我们旨在评估 hAEC 是否可以修复由博莱霉素在小鼠中诱导的现有肺部损伤，以及细胞给药的时间是否会影响修复效果。此外，我们旨在研究 hAEC 对成纤维细胞增殖和激活的影响，以研究可能的修复作用机制。 hAEC 经腹腔（IP）给药，在博莱霉素暴露后 7 或 14 天。在 hAEC 给药后 7 天评估肺部。博莱霉素在 14 天和 21 天明显降低体重并引起肺部炎症和纤维化。在博莱霉素后 7 天给予 hAEC 对肺损伤没有影响，而在博莱霉素后 14 天给予 hAEC 则使肺组织密度，胶原蛋白含量和α-SMA 的产生正常化，同时减少了肺白细胞和肺 TGF-β，PDGF-α和 PDGF-β的表达。在体外，hAEC 减少了原代小鼠肺成纤维细胞的增殖和激活。我们的发现表明，在肺部疾病过程中 hAEC 给药的时间可能会影响 hAEC 修复肺损伤的能力。
