Acute Lung Injury: Making Injured Lungs Perform Better and Rebuilding Healthy Lungs

摘要

Acute lung injury (ALI) is a complex condition associated with diffuse injury to the alveolar epithelial gas exchange surface, resulting in marked impairment in the ability to oxygenate blood. The goal of our application is to develop ventilatory and cell based strategies to treat the ALI syndromes that complicate cancer care. As we have previously noted, ALI is associated with severe infections, exposure to toxins, trauma, and multiple blood transfusions. Cancer patients are particularly vulnerable to development of ALI as a result of the immunosuppressive effects of chemotherapy and the debilitating effects of cancer. Of note, military personnel are also at risk for development of ALI because of battle induced trauma and the consequent need for blood transfusions. In Project 1, we proposed to develop a novel mode of ventilation (variable ventilation) that will minimize the toxic effects of conventional mechanical ventilation in patients with ALI. We have completed various types of in vitro and in silico analysis of variable ventilation, and a result, are nearly ready to commence a clinical study. In the preclinical Project 2 study in mice, we have been optimizing the derivation of progenitor cells that can be administered to mice with ALI with the intent of reconstituting the damaged gas exchange surface. Our data suggest that iPS may be most suitable for this purpose. To summarize in the past year, we have: 1) successfully developed the necessary software for variable ventilation 2) continued the process of submitting an IND application to begin a Phase I study of variable ventilation, 2) and optimized derivation of mouse stem cells for testing in mice with ALI.