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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Allogeneic human mesenchymal stem cells for treatment of E. coli endotoxin-induced acute lung injury in the ex vivo perfused human lung
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Allogeneic human mesenchymal stem cells for treatment of E. coli endotoxin-induced acute lung injury in the ex vivo perfused human lung

机译:同种异体人间充质干细胞在离体灌注人肺中治疗大肠杆菌内毒素诱导的急性肺损伤

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摘要

Recent studies have suggested that bone marrow-derived multi-potent mesenchymal stem cells (MSCs) may have therapeutic applications in multiple clinical disorders including myocardial infarction, diabetes, sepsis, and hepatic and acute renal failure. Here, we tested the therapeutic capacity of human MSCs to restore alveolar epithelial fluid transport and lung fluid balance from acute lung injury (ALI) in an ex vivo perfused human lung preparation injured by E. coli endotoxin. Intra-bronchial instillation of endo-toxin into the distal airspaces resulted in pulmonary edema with the loss of alveolar epithelial fluid transport measured as alveolar fluid clearance. Treatment with allogeneic human MSCs or its conditioned medium given 1 h following endotoxin-induced lung injury reduced extravascular lung water, improved lung endothe-lial barrier permeability and restored alveolar fluid clearance. Using siRNA knockdown of potential paracrine soluble factors, secretion of keratinocyte growth factor was essential for the beneficial effect of MSCs on alveolar epithelial fluid transport, in part by restoring amiloride-dependent sodium transport. In summary, treatment with allogeneic human MSCs or the conditioned medium restores normal fluid balance in an ex vivo perfused human lung injured by E. coli endotoxin.
机译:最近的研究表明,骨髓源性多能间充质干细胞(MSC)可能在多种临床疾病中具有治疗应用,包括心肌梗塞,糖尿病,败血症以及肝和急性肾功能衰竭。在这里,我们测试了人间充质干细胞在由大肠杆菌内毒素损伤的离体灌注人肺制剂中,从急性肺损伤(ALI)恢复肺泡上皮液运输和肺液平衡的治疗能力。支气管内内毒素向远端空域的滴注导致肺水肿,肺泡上皮液运输的损失以肺泡液清除率衡量。内毒素诱导的肺损伤后1小时给予同种异体人MSC或其条件培养基进行治疗,可减少血管外肺水,改善肺内皮-内皮屏障通透性并恢复肺泡液清除率。使用潜在的旁分泌可溶性因子的siRNA敲除,角质形成细胞生长因子的分泌对于MSC对肺泡上皮液运输的有益作用至关重要,其部分原因是通过恢复阿米洛利依赖的钠运输。总之,用同种异体人MSC或条件培养基进行的治疗可恢复被大肠杆菌内毒素损伤的离体灌注人肺中的正常液体平衡。

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  • 作者单位

    Department of Anesthesiology, University of California, San Francisco, CA 94143 University of California San Francisco, Department of Anesthesiology, 505 Parnassus Avenue, Box 0648, San Francisco, CA 94143;

    Cardiovascular Research Institute, University of California, San Francisco, CA 94143;

    Division of Pulmonary and Critical Care, University of California, San Francisco, CA 94143;

    Children's Hospital Oakland Research Institute, Oakland, CA 94609;

    Department of Anesthesiology, University of California, San Francisco, CA 94143 Cardiovascular Research Institute, University of California, San Francisco, CA 94143 Division of Pulmonary and Critical Care, University of California, San Francisco, CA 94143;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    alveolar fluid clearance; keratinocyte growth factor; pulmonary edema; acute respiratory distress syndrome;

    机译:肺泡液清除率;角质形成细胞生长因子肺水肿;急性呼吸窘迫综合征;

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