This proposal is focused on developing bone marrow derived mesenchymal stem cells (MSCs) as a therapy for critically ill patients who have severe pneumonia leading to lung injury and an overwhelming bloodstream infection (sepsis). This syndrome is the most common cause of death among patients in Intensive Care Units, and it carries a mortality rate of 40-50% despite the best supportive care and accounts for over 200,000 deaths/year. New therapies are urgently needed.
MSCs are adult stem cells usually obtained from the bone marrow that have been demonstrated to have significant protective effects in experimental models of severe lung injury and sepsis. MSCs work by reducing excessive inflammation, promoting the clearance of bacteria, and facilitating the repair of injured organ tissues.
The studies in this proposal will use validated, clinical grade MSCs in a mouse model of severe lung injury and sepsis to help answer important remaining questions in the effort to develop MSCs a therapy for critically ill patients. Specifically, it will determine the optimal growth conditions for MSCs, the optimal manner in which MSCs should be delivered to patients, and whether purified proteins obtained from MSCs can achieve protection similar to using live cells. The results from these experiments will significantly enhance our ability to develop the most optimal MSC based therapy for patients with severe lung injury and sepsis that can be tested in a clinical trial.
Public Health Benefit. The proposed research aims to develop a novel, stem cell based therapy for critically ill patients who have severe lung injury and sepsis from bacterial pneumonia. This is the most common cause of death among critically ill patients with a mortality rate of 40-50% despite the best, current supportive care. The incidence and severity of this syndrome is expected to increase as the population of California and the nation increases. Furthermore, antibiotic resistance has significantly hampered the treatment of patients with this clinical disease, and the need for new forms of therapy is high. Therefore, this proposal will provide significant potential benefit to the citizens of California by helping to treat this important public health problem.
Economic Benefit. During the current economic climate in California and the nation, the impact that an investment such as the current CIRM program has on improving the employment potential of Californians is important to consider. As part of this proposal, new personnel will be hired to help in the completion of the studies. These individuals, along with the principal investigator, will become part of a highly trained group of investigators that will help create a sustainable program of innovative stem cell research for patients in California who have lung disease.