Acute lung injury is a major cause of acute respiratory failure than develops in adult and pediatric critically ill patients following major trauma and shock, severe pneumonia, sepsis, and aspiration syndromes. Mortality from acute lung injury is high, with approximately 75,000 deaths per year in the United States alone. Also, most patients who recover from this cause of respiratory failure require extended rehabilitation, although the longer term prognosis for return to normal lung function in survivors is excellent. There has been some progress in treatment of victims of acute lung injury. For example, lung protective mechanical ventilation strategies have improved clinical outcomes. However, there is no specific drug or other treatment that can reduce lung injury and mortality. Based on recent experimental studies from several investigators, allogeneic mesenchymal stem cells are effective for reversing acute lung injury and improving survival in animal models. There is also evidence that intrapulmonary administration of allogeneic human mesenchymal cells induces a nearly complete reversal of acute lung injury in an ex vivo perfused human lung preparation. Thus, there is a major opportunity to translate allogeneic human mesenchymal stem cells to clinical trials in patients with acute lung injury. A well organized planning program is needed to integrate both basic and clinical scientists from several California universities and private institutions with the objective of developing an effective and efficient network for translating mesenchymal stem cell studies to patients with acute lung injury. Faculty and staff from California institutions with expertise in immunology, cell based therapeutics, and clinical trials will form the core team to combine their expertise in preclinical and clinical studies to develop a plan for testing the safety and the effectiveness of allogeneic mesenchymal stem cells in patients with lung injury. Industrial partners with expertise and experience in the clinical use of cell based therapies will also be included in the team. The planning work will use a certified Good Medical Practice facility to culture and grow allogeneic mesenchymal stem cells from normal donors, and test them for safety for human use, as well as to evaluate their biological activity. The final planning product from this Disease Team Planning effort will include specific milestones for meeting the FDA regulatory steps to obtain approval for evaluating mesenchymal stems cells in critically ill patients with acute lung injury. At the end of the 6 month planning period, there will be detailed plans for evaluation this promising new therapy in critically ill patients with acute lung injury at 6 California hospitals.
Statement of Benefit to California:
Acute lung injury is a common cause of acute respiratory failure in critically ill patients. Based on recent studies, acute lung injury occurs annually in approximately 24,000 patients in California alone with an estimated mortality of 40% in those patients. Acute lung injury can develop in normal individuals who have been injured in major trauma, such as following an automobile accident or from exposure to smoke fumes in a fire. It also can occur in otherwise normal individuals who develop severe pneumonia from a viral infection, such as the flu. Acute lung injury also develops in patients with a variety of chronic medical illnesses including diabetes, chronic lung diseases, liver disease and dialysis dependent kidney failure. Acute lung injury develops in both pediatric and adult patients and treatment is required in an intensive care unit where patients can receive life support with mechanical ventilation and other life saving therapies. In spite of progress in supportive care for this syndrome of acute respiratory failure, 40% of patients with acute lung injury do not survive. Also, the patients who do survive require long periods of hospitalization to recover and also require extended periods of rehabilitation in specialized facilities. Thus, the emotional, social, financial and economic costs to the citizens of California is high, and therefore innovative approaches to treatment of acute lung injury are needed. New evidence indicates that allogeneic mesenchymal stem cells can potentially provide an effective and safe new treatment for both children and adults with this syndrome of severe acute respiratory failure. By forming a California based team of basic and clinical investigators from universities and industry, we can develop a comprehensive plan to develop and test this new therapy for acute lung injury patients. The first anticipated benefit will be an increased survival in California residents who develop this form of acute respiratory failure. The second anticipated benefit be a reduction in the need for life support in an intensive care unit, leading to more rapid rehabilitation and return to productive, independent lives.