Expanding the lung donor pool: interventions to improve donor management, expand ex vivo lung perfusion and repair injured donor lungs
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.
The overarching of the research project is to develop strategies to treat ARDS after brain injury and to expand the donor lung pool for transplantation. Our strategic approach is to study innate immune dysfunction after brain injury and in the ex vivo perfused human lung. Our hypothesis is that modulating innate immune dysfunction after brain injury, using mesenchymal stromal cells and specialized pro-resolving mediators, will allow us to effectively enhance lung repair. Three aims will test the hypothesis by molecular and physiologic investigations, in patients with Acute Brain Injury and in the human EVLP mode.
- Award Date
- 14 February 2020
- Award Value
- €774,760.00
- Principal Investigator
- Professor Gerard Curley
- Host Institution
- Royal College of Surgeons in Ireland
- Scheme
- Emerging Clinician Scientist Awards 2020