Mesenchymal Stem Cells for Treatment of ARDS Following Trauma
Abstract
Acute respiratory distress syndrome (ARDS) is a life-threatening medical condition in which the lung is injured or inflamed to the degree that it cannot properly exchange gases and oxygenate the body. ARDS can be caused by a variety of conditions including infections, trauma, severe blood loss, multiple or large volume blood transfusions, burns, and the inhalation of chemical poisons or smoke. According to the National Heart Lung and Blood Institute, approximately 190,000 people in the U.S. develop ARDS each year. Even with state-of-the-art supportive care with optimal lung protective mechanical ventilation, the death rate from ARDS ranges from 25% to 40%, with higher rates seen in less technologically developed areas. Recent studies from the Department of Defense Iraq Trauma Registry (DoDTR) reported that ARDS developed in a large number of severely wounded Warfighters and was associated with higher death rates. To date, there have been few advances in the treatment of major trauma-related conditions such as ARDS. The development of new therapeutics that can limit the severity and/or progression of lung injuries that lead to ARDS and death is an immediate clinical need in both military and civilian sectors. Experimental studies carried out in small and large animals have demonstrated that specialized cells called mesenchymal stem cells (MSC) can effectively reduce inflammation in multiple diseases including ARDS. In a Phase 1 clinical trial in patients with ARDS from medical causes, MSC were found to be safe and well tolerated, paving the way for additional clinical studies. Currently there is a Phase 2 civilian study in progress investigating the therapeutic potential of MSC; however, the study does not include trauma patients. This proposal aims to test the therapeutic potential of MSC in patients with trauma-induced ARDS. MSC have the potential to decrease disability and death in trauma patients from both civilian and military settings. The overall objective of this proposal is to carry out a randomized, double-blinded, placebo-controlled, multicenter Phase 2b trial to test the therapeutic potential of allogeneic bone-marrow derived MSC for treating ARDS in trauma patients. The specific aims of this grant are: Specific Aim 1: To test the clinical efficacy of intravenously delivered allogeneic human MSC in trauma patients with ARDS. Specific Aim 2: To test the mechanisms by which MSC reduce acute lung injury in trauma patients with ARDS.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1710631
Entities
People
- Michael Matthay
Organizations
- United States Army
- University of California, San Francisco