When people sustain injury to the brain after a fall, road traffic accident, or major brain bleed, they require care in an Intensive Care Unit. After major brain injury, a patient’s lungs also often fail – this is termed “Acute Respiratory Distress Syndrome” (ARDS). ARDS after brain injury is common and contributes significantly to poor outcomes and death. There are no treatments available for ARDS. Two of the reasons that explain this are: the relative inaccessibility of the lung, which makes it difficult to study, and an over-reliance on animal models of disease. We propose to overcome these problems by studying the development of ARDS in patients with brain injury, and by using human lungs from brain-injured donors that have been rejected for transplantation as tools for research into how the lung works and specifically how immune cells in the blood and lung respond to brain and lung injury. We will keep the lungs alive after they have been removed by circulating a blood-based fluid through the lung’s blood supply and by gently inflating them using a ventilator identical to that used to treat patients in intensive care. Under these conditions we can observe the lung response to promising treatments. Research from our group suggests that Mesenchymal Stem Cells (MSCs) offer significant hope for ARDS. MSCs can be obtained from bone marrow and umbilical cord and are highly effective in our preclinical ARDS models. We propose to use MSCs, and the products that they secrete separately, to treat ARDS in our human lung model. A therapy that reduces the severity of ARDS is badly needed. If we are successful, we will conduct a larger clinical study to determine whether MSCs, or the products that MSCs secrete, reduce the severity of ARDS and improve the quality of organs available for transplantation.
