Allogeneic human mesenchymal stem cells for treatment of E. Coli endotoxin‐induced acute lung injury in an ex vivo perfused human lung

Abstract

Recent studies have indicated that bone marrow derived mesenchymal stem cells (MSC) may have therapeutic applications in multiple clinical disorders. Currently, little is known regarding the effect of MSC in experimental models of acute lung injury (ALI) and pulmonary edema. We recently reported that intrapulmonary (via the trachea) treatment with MSC 4 h after endotoxin delivery to the lung improved survival and reduced the extent of pulmonary edema formation in endotoxin‐induced ALI in mice (J Immunol 2007). Here, we tested the therapeutic potential of human MSC to resolve pulmonary edema from ALI in an ex vivo perfused human lung preparation injured by E. Coli endotoxin. Intra‐bronchial instillation of endotoxin resulted in the loss of alveolar epithelial fluid transport measured as alveolar fluid clearance (AFC). Instillation of allogeneic human MSC or its conditioned medium given 1 h following endotoxin‐induced lung injury completely restored AFC. Using siRNA knockdown of potential paracrine soluble factors, we found that the secretion of keratinocyte growth factor (KGF) was essential for the restorative effect of MSC. In summary, the therapeutic effect of allogeneic human MSC on the resolution of endotoxin‐induced pulmonary edema in an ex vivo perfused human lung was mediated by the secretion of KGF. FAER & NHLBI HL093026, HL51854 and HL51856.