Mesenchymal Stem Cells: A Promising Therapy for the Acute Respiratory Distress Syndrome

Abstract

Acute respiratory distress syndrome (ARDS) is a pulmonary syndrome with growing prevalence and high mortality and morbidity that increase with age. There is no current therapy able to restore pulmonary function in ARDS patients. Preclinical models of ARDS have demonstrated that intratracheal or systemic administration of mesenchymal stem cells (MSCs) protects the lung against injury. The mechanisms responsible for the protective effects are multiple, including the secretion of multiple paracrine factors capable of modulating the immune response and restoring epithelial and endothelial integrity. Recent studies have demonstrated that MSCs can also control oxidative stress, transfer functional mitochondria to the damaged cells, and control bacterial infection by secretion of antibacterial peptides. These characteristics make MSCs promising candidates for ARDS therapy.

Advances in Understanding of the Pathogenesis of Acute Respiratory Distress Syndrome

“…The paradigm has previously been that AT2 cells are the source of new AT1 cells; however, there is evidence that a separate cell population, with distinct cell surface markers and lacking surfactant protein C expression, may be pluripotential for differentiation to either AT1 or AT2 cells [134]. This has led to studies exploring the therapeutic potential of stem cell therapies in ARDS, which have rapidly reached clinical trials [135,136]. This area is beyond the scope of this review.…”

Lipopolysaccharide Impaired the Functional Activity of Endothelial Colony-Forming Cells

“…Recently, associations between early EPCs and chronic obstructive pulmonary disease [11], ALI [12] and bacterial pneumonia [13] have been reported. More recently, relationships between stem cells, progenitor cells and lung diseases have been widely discussed [14,15,16]. Furthermore, infusion of LPS led to a significant decrease in peripheral early EPCs in humans [17].…”

Mesenchymal stem cells for therapy in lung diseases

“…Lung conditions and systemic diseases that affect the lung through the bloodstream are associated with the development of ARDS, and the disease encompasses an increase in alveolar and vascular permeability (mediated by endothelin-1, phospholipase A2, and angiotensin-2), loss of epithelial integrity, influx of inflammatory cells (IL-1β, TNF-α, and IL-6), and formation of hyaline membranes in a complex process that frequently ends in multiple organ failure as a cause of death (16). The Berlin definition (26) set the new diagnosis criteria for ARDS based on: timing (within one week of clinical insult or new or worsening respiratory symptoms), radiography (bilateral opacities not fully explained by effusions, lobar/lung collapse, or nodules), origin of edema (respiratory failure not fully explained by cardiac failure or fluid overload), and oxygenation impairment (mild: 200 mmHg < PaO2/FiO2 <300 mmHg, moderate: 100 mmHg < PaO2/FiO2 200 <mmHg, and severe: PaO2/FiO2 <100 mmHg).…”

“…The Berlin definition (26) set the new diagnosis criteria for ARDS based on: timing (within one week of clinical insult or new or worsening respiratory symptoms), radiography (bilateral opacities not fully explained by effusions, lobar/lung collapse, or nodules), origin of edema (respiratory failure not fully explained by cardiac failure or fluid overload), and oxygenation impairment (mild: 200 mmHg < PaO2/FiO2 <300 mmHg, moderate: 100 mmHg < PaO2/FiO2 200 <mmHg, and severe: PaO2/FiO2 <100 mmHg). Thus, according to this definition, the term "acute lung injury" as used previously now falls in the category of moderate ARDS (16,26). Despite the increased interest in reaching a curative treatment for this condition, the current therapies focus on supportive care techniques of lung protective ventilation and a conservative fluid strategy (27), and there is not a proven therapy to reduce the severity of lung injury or to improve the outcomes.…”

“…Different studies have demonstrated the proliferative potential of MSCs through the secretion of cytokines and growth factors using murine (28) and large animal (29,30) models of endotoxin-induced ARDS. These experiments revealed a decrease in proinflammatory cytokines, increase in anti-inflammatory cytokines, histological decrease in lung injury, and overall increase in survival rates (16,20,(28)(29)(30)(31)(32)(33)(34). Our group has demonstrated that infusion of MSCs prevents the inflammatory response to endotoxin and attenuates the lung injury, protecting as well against pulmonary edema (7).…”