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Cell-based therapies for lung vascular diseases: lessons for the future.

Pulmonary arterial hypertension or acute respiratory distress syndrome (ARDS) represent diseases caused in large part by lung endothelial injury and inflammation. Pulmonary arterial hypertension is a progressive and debilitating lung disorder, which is characterized by hallmark pathological features in the small peripheral pulmonary arteries, including intimal hyperplasia and fibrosis, medial hypertrophy, increased deposition of extracellular matrix, infiltration of inflammatory mediators, and in many instances of advanced disease, plexiform lesions. ARDS is a clinically important complication of severe acute lung injury and a significant cause of morbidity and mortality in critically ill patients. Acute lung injury/ARDS is characterized by breakdown of the air-blood barrier, with the accumulation of proteinaceous fluid and influx of inflammatory cells into the alveolar airspace, all of which are likely mediated by endothelial dysfunction and disruption of the pulmonary endothelial barrier. Preclinical studies suggest that cellular therapies may offer unique and effective alternatives for respiratory diseases that currently have limited (or no) treatment options. Encouraging results from studies using progenitor or mesenchymal stem cells suggest that these cells may exert their therapeutic benefits by promoting vascular repair and regeneration and/or by modulating the pathological immune responses. Furthermore, by combining genetic engineering with cell therapy, it may be possible to enhance the regenerative function of these cells, particularly in the context of adult autologous cell therapy, and therefore provide additional benefits that may overcome many of the limitations of cell or gene therapy alone.