Michael Matthay, MD

Core

My research group is focused on understanding the mechanisms of experimental and human acute lung injury and developing novel therapeutics for this syndrome. Acute Lung Injury/Acute Respiratory Distress Syndrome (ALI/ARDS) is a common form of hypoxemic respiratory failure in critically ill patients that has a mortality of 30-40% despite the best supportive care. As of now, the only interventions that have been proven to be of benefit in managing ALI/ARDS include supportive measures such as low-tidal volume ventilation and a conservative approach to fluid management. Therefore, there is a pressing need for new therapies for this syndrome.

We have developed many experimental models in which we can study the mechanisms of acute lung injury and test novel therapies. These include infectious models such as endotoxin and E. coli induced lung injury and non-infectious models such as acid induced and transfusion related lung injury. Using the model for transfusion related lung injury, the most common cause of mortality from transfusions, we have been able to determine the basic mechanisms responsible for its pathogenesis (Looney, 2006). In addition, we have tested novel therapeutic agents such as nicotine in the acid induced model of ALI and have demonstrated its protective effects through the alpha7 nicotonic receptor (Su, 2007).

More recently, we have focused on understanding the effects of mesenchymal stem cells in experimental models of ALI. Bone marrow derived mesenchymal stem cells are a type of adult stem cell that have potent immunomodulatory properties. Using the endotoxin model of ALI, we have been able to demonstrate that treatment with mesenchymal stem cells improves survival and reduces the severity of endotoxin induced lung injury (Gupta, 2007). This protection is related, in part, to the ability of the cells to shift the response to endotoxin from a pro to an anti-inflammatory process. These results offer promise for the use of cell based therapy for the treatment of ALI/ARDS, and currently we are developing pre-clinical models in which to test the effects of human mesenchymal stem cells.