Acute lung injury (ALI) is a common lung disorder that affects millions of people every year. The infiltration of inflammatory cells into the lungs and death of the alveolar epithelial cells are key factors to trigger a pathological cascade. Trophoblast stem cells (TSCs) are immune privileged, and demonstrate the capability of self-renewal and multipotency with differentiation into three germ layers. We hypothesized that intratracheal transplantation of TSCs may alleviate ALI. ALI was induced by intratracheal delivery of bleomycin (BLM) in mice. After exposure to BLM, pre-labeled TSCs or fibroblasts (FBs) were intratracheally administered into the lungs. Analyses of the lungs were performed for inflammatory infiltrates, cell apoptosis, and engraftment of TSCs. Pro-inflammatory cytokines/chemokines of lung tissue and in bronchoalveolar lavage fluid (BALF) were also assessed. The lungs displayed a reduction in cellularity, with decreased CD45+ cells, and less thickening of the alveolar walls in ALI mice that received TSCs compared with ALI mice receiving PBS or FBs. TSCs decreased infiltration of neutrophils and macrophages, and the expression of interleukin (IL) 6, monocyte chemoattractant protein-1 (MCP-1) and keratinocyte-derived chemokine (KC) in the injured lungs. The levels of inflammatory cytokines in BALF, particularly IL-6, were decreased in ALI mice receiving TSCs, compared to ALI mice that received PBS or FBs. TSCs also significantly reduced BLM-induced apoptosis of alveolar epithelial cells in vitro and in vivo. Transplanted TSCs integrated into the alveolar walls and expressed aquaporin 5 and prosurfactant protein C, markers for alveolar epithelial type I and II cells, respectively. Intratracheal transplantation of TSCs into the lungs of mice after acute exposure to BLM reduced pulmonary inflammation and cell death. Furthermore, TSCs engrafted into the alveolar walls to form alveolar epithelial type I and II cells. These data support the use of TSCs for the treatment of ALI.

中文翻译：

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滋养层干细胞气管内移植减轻小鼠急性肺损伤

急性肺损伤 (ALI) 是一种常见的肺部疾病，每年影响数百万人。炎症细胞浸润到肺和肺泡上皮细胞死亡是触发病理级联反应的关键因素。滋养层干细胞 (TSC) 具有免疫特权，并表现出自我更新和多能分化成三个胚层的能力。我们假设 TSC 的气管内移植可以缓解 ALI。ALI 是由小鼠气管内输送博来霉素 (BLM) 诱导的。暴露于 BLM 后，将预先标记的 TSC 或成纤维细胞 (FB) 经气管内给药到肺部。对肺部进行了炎症浸润、细胞凋亡和 TSC 植入的分析。还评估了肺组织和支气管肺泡灌洗液 (BALF) 中的促炎细胞因子/趋化因子。与接受 PBS 或 FB 的 ALI 小鼠相比，接受 TSC 的 ALI 小鼠的肺细胞结构减少，CD45+ 细胞减少，肺泡壁增厚较少。TSCs 减少了中性粒细胞和巨噬细胞的浸润，以及白细胞介素 (IL) 6、单核细胞趋化蛋白 1 (MCP-1) 和角质形成细胞衍生趋化因子 (KC) 在受损肺中的表达。与接受 PBS 或 FB 的 ALI 小鼠相比，接受 TSC 的 ALI 小鼠的 BALF 中炎性细胞因子，特别是 IL-6 的水平降低。TSC 在体外和体内也显着降低 BLM 诱导的肺泡上皮细胞凋亡。移植的 TSC 整合到肺泡壁中并分别表达水通道蛋白 5 和前表面活性蛋白 C，它们分别是肺泡上皮 I 型和 II 型细胞的标志物。在急性暴露于 BLM 后，将 TSCs 气管内移植到小鼠肺部可减少肺部炎症和细胞死亡。此外，TSCs 植入肺泡壁形成肺泡上皮 I 型和 II 型细胞。这些数据支持使用 TSC 治疗 ALI。