ACUTE RESPIRATORY DISTRESS SYNDROME
Acute Respiratory Distress Syndrome (ARDS) is defined by the acute onset of non-cardiogenic pulmonary edema, hypoxia and the need for mechanical ventilation. In the current pandemic, ARDS is a major complication of coronavirus disease-19 (COVID-19) and is associated with significant long-term morbidity and mortality. Our research focuses on how MSCs and MSC-EVs can regenerate the damaged lung, restore the epithelial-endothelial barrier and restore the bioenergetic health of injured cells.
Acute Respiratory Distress Syndrome
ARDS consists of acute respiratory failure with progressive arterial hypoxia, shortness of breath, and an increased work of breathing, thus requiring most patients to need endotracheal intubation and positive pressure ventilation. Each year in the United States, ARDS affects approximately 200,000 adult patients with a mortality of approximately 40% given that the standard of care is mostly supportive; though these statistics are currently much higher in the present pandemic caused by COVID-19.
In the acute phase of ARDS (the first 1–6 days), there is interstitial and alveolar edema with accumulation of neutrophils, macrophages and red blood cells with evidence of endothelial and epithelial injury. In the subacute phase (the next 7–14 days), the edema subsides and there is evidence of organ repair with alveolar epithelial type II cell proliferation. In addition, there is infiltration of fibroblasts resulting in collagen deposition. In the chronic phase (after 14 days), the neutrophilic infiltrate resolves and is replaced by mononuclear cells and alveolar macrophages within the alveoli. Furthermore, there is evidence of alveolar epithelial
epithelial repair as well as fibrosis. Recent clinical studies have shown that MSCs are useful to treat patients with ARDS based on their ability to prevent or attenuate the immunopathogenic cytokine storm while also promoting tissue/alveolar repair. Hence, our lab is currently examining ways to optimize MSCs and MSC-EVs for the treatment of ARDS and understanding their mechanisms of action, especially given the implications of ARDS in the setting of COVID-19.