Allogeneic human mesenchymal stem cells for treatment of E. coli endotoxin-induced acute lung injury in the ex vivo perfused human lung.

Abstract

Recent studies have suggested that bone marrow-derived multipotent 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 endotoxin 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 endothelial 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.

• Authors: Jae W Lee, Xiaohui Fang, Naveen Gupta, Vladimir Serikov, Michael A Matthay
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 106 Issue 38 Pg. 16357-62 (Sep 22 2009) ISSN: 1091-6490 [Electronic] United States
• PMID: 19721001 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Culture Media, Conditioned
• Endotoxins
• FGF7 protein, human
• Recombinant Proteins
• Sodium Channel Blockers
• Fibroblast Growth Factor 7
• Amiloride

Topics

• Acute Disease
• Adult
• Amiloride (pharmacology)
• Body Fluids (metabolism)
• Cells, Cultured
• Culture Media, Conditioned (pharmacology)
• Endotoxins
• Escherichia coli (chemistry)
• Female
• Fibroblast Growth Factor 7 (genetics, pharmacology)
• Humans
• In Vitro Techniques
• Leukocyte Count
• Lung (metabolism, pathology, surgery)
• Lung Injury (chemically induced, surgery)
• Male
• Mesenchymal Stem Cell Transplantation (methods)
• Mesenchymal Stem Cells (cytology, metabolism)
• Middle Aged
• Neutrophils (pathology)
• Perfusion
• Pulmonary Alveoli (drug effects, metabolism)
• Pulmonary Edema (metabolism, pathology, prevention & control)
• Recombinant Proteins (pharmacology)
• Sodium Channel Blockers (pharmacology)
• Transplantation, Homologous