关键词：肺;干细胞;创伤和损伤;肿瘤;细胞(生物学);临床医学,计算机编程
摘 要：Acute lung injury (ALI) is a complex condition associated with diffuse injury to the distal alveolar epithelial gas exchange surface, resulting in marked impairment in the ability to oxygenate blood. This condition commonly afflicts patients with cancer. In this regard, cancer patients are especially susceptible to developing ALI due to the immunosuppressive and toxic effects of chemotherapy and the debilitating effects of cancer. The over-arching goal of our application is to develop ventilatory and cell based strategies to treat the ALI syndromes. In Project 1, we proposed to develop a novel mode of ventilation (variable ventilation) that will minimize the injurious effects of conventional mechanical ventilation in patients with ALI. In the past year, we have successfully developed software to allow for programming the titration of inspiratory flow and inspiratory time on the ventilator to patient comfort for variable ventilation. Most notably, we have obtained an approved IND from the FDA to proceed with the human study as originally proposed. To proceed, we plan to submit and obtain approval of the FDA s required changes in our protocol with our local institutional IRB. Once this has been achieved, we will request DoD human subjects review and approval. In the preclinical Project 2 we proposed to develop a cell based therapy for ALI. In the past year, we have successfully developed protocols for the differentiation of embryonic stem cells into distal lung alveolar epithelial cells. . These cells were found to engraft in a de-cellularized lung preparation with the morphological appearance of alveolar epithelium. In the future, we hope to utilize these derivative lung epithelial cells to treat ALI induced in mice.