Michael Biskup

Introduction. Acute Respiratory Distress Syndrome (ARDS) is an inflammatory reaction of the lungs to cellular damage. ARDS commonly develops after trauma, infection, pleuritis, and aspiration. Hypoxemic respiratory failure is a defining characteristic. In the beginning stages of ARDS, the body releases inflammatory mediators such as IL-1. Neutrophils then migrate into alveoli and release cytokines, proteases, and reactive oxygen species (ROS). Alveolar capillaries and endothelial cells become damaged leading to diffuse alveolar damage. Exudate accumulates in the interstitium and alveolar surface leading to pulmonary edema. Alveolar hyaline membranes form and damage to pneumocytes leads to alveolar collapse¹. Treatment of ARDS includes intubation and mechanical ventilation with saturated O₂, or ECMO in extreme cases, as well as corticosteroids and other medications¹. ARDS makes up 10.4%² of ICU admissions, yet mortality is 40%³. The latest research in ARDS involves mesenchymal stem cells (MSCs). Multipotent stem cells can differentiate into many cells and have shown immunomodulatory effects in ARDS animal models. Methods. Three animal studies will be discussed. The first two^4,5 involved injecting lipopolysaccharide (LPS) into the lungs of mice resulting in ARDS. Mice were divided into experimental groups receiving MSC treatment and control groups receiving no treatment. Various aspects of the disease process were compared between the groups. In the third animal study⁶, VEGF knockout MSCs were administered with LPS into experimental mice, while control mice received normal MSCs and LPS. The difference in pathogenesis was studied between groups. Results. The first study showed several ways that MSCs dampen the host immune response. The experimental mice group had greater inhibition of macrophages within lung tissue, higher IL-10 levels, decreased Th1 response, greater paracrine signaling of prostaglandin E2, higher GM-CSF, higher 1L-6, higher IL-13, and decreased Th2 response⁴. The second animal study’s experimental group exhibited decreased ROS concentrations, decreased oxidative burst in neutrophils and macrophages, and decreased neutrophil extracellular traps in lung tissue⁵. The third animal study illustrated that the controls had less permeability, inflammation, and epithelial cell apoptosis within the lung⁶. Conclusion. MSCs attenuate the mouse immune response in the setting of ARDS in several ways. They dampen cell-mediated and humoral immune responses via inhibition of Th1 cells, Th2 cells, macrophages, and neutrophils. Furthermore, MSCs release VEGF which protects lung tissue from inflammation in ARDS. These findings warrant further investigation for the use of MSCs in the treatment of ARDS in humans.

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