Human Amnion Epithelial Cells Prevent Bleomycin-Induced Lung Injury and Preserve Lung Function
Human Amnion Epithelial Cells Prevent Bleomycin-Induced Lung Injury and Preserve Lung Function
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DOI：
10.3727/096368910x543385
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发表时间：
2011-01-01
影响因子：
3.3
通讯作者：
Wallace, Euan
中科院分区：
文献类型：
--
作者：
Murphy, Sean;Lim, Rebecca;Wallace, Euan
人羊膜上皮细胞（Human amnion epithelial cells，hAEC）作为再生治疗的有希望的细胞来源最近引起了关注，有报道称来源于人足月羊膜的细胞具有多能分化能力、低免疫原性和抗炎特性。具体地，在以继发于慢性炎症和纤维化的肺组织的显著损失为特征的肺病的动物模型中，hAEC的移植已经显示出减少炎症和随后的纤维化。为了进一步探索hAEC减少肺纤维化和增强肺再生的机制，我们利用博来霉素诱导的肺纤维化模型并研究hAEC减少纤维化从而改善肺功能的能力。我们的目的是确定hAECs，注射到腹膜腔中，是否可以迁移到肺，植入，并形成功能性肺上皮，以及hAECs是否可以调节博莱霉素损伤的肺中的炎症环境。我们证明，与单独的博来霉素相比，博来霉素后24小时IP施用hAEC降低了促炎细胞因子TNF-α、TGF-β、IFN-γ和IL-6的基因表达，并降低了随后的肺纤维化，肺胶原沉积减少，α-平滑肌肌动蛋白水平降低，炎性细胞浸润减少。我们还表明，hAEC能够预防与博来霉素诱导的肺损伤相关的肺功能下降。在给药后，我们无法检测到hAEC在受损或未受损肺中的任何显著植入。这项研究的结果支持进一步研究hAECs作为炎症和纤维化疾病的潜在细胞疗法。
Human amnion epithelial cells (hAECs) have attracted recent attention as a promising source of cells for regenerative therapies, with reports that cells derived from human term amnion possess multipotent differentiation ability, low immunogenicity, and anti-inflammatory properties. Specifically, in animal models of lung disease characterized by significant loss of lung tissue secondary to chronic inflammation and fibrosis, the transplantation of hAECs has been shown to reduce both inflammation and subsequent fibrosis. To further explore the mechanisms by which hAECs reduce pulmonary fibrosis and enhance lung regeneration, we utilized a bleomycin-induced model of pulmonary fibrosis and investigated the ability of hAECs to reduce fibrosis and thereby improve pulmonary function. We aimed to determine if hAECs, injected into the peritoneal cavity could migrate to the lung, engraft, and form functional lung epithelium, and whether hAECs could modulate the inflammatory environment in the bleomycin-injured lung. We demonstrated that, compared to bleomycin alone, IP administration of hAECs 24 h after bleomcyin, decreased gene expression of the proinflammatory cytokines TNF-alpha, TGF-beta, IFN-gamma, and IL-6 and decreased subsequent pulmonary fibrosis with less pulmonary collagen deposition, reduced levels of a-smooth muscle actin and decreased inflammatory cell infiltrate. We also showed that hAECs are able to prevent a decline in pulmonary function associated with bleomycin-induced lung damage. We were unable to detect any significant engraftment of hAECs in injured, or uninjured, lung after administration. The findings from this study support the further investigation of hAECs as a potential cell therapy for inflammatory and fibrogenic diseases.