Human Mesenchymal Stromal Cells for Respiratory Distress Syndrome

The signs of respiratory distress syndrome are not one size fits all, with variations in signs as well as the presence of the severity of respiratory distress syndrome, patient age, and underlying medical disease. Patients with underlying conditions, such as lung injury or trauma, or those who are more frail, are at a higher risk of respiratory distress syndrome. Patients may have signs of respiratory distress syndrome in 1 or more vital signs, and be discharged from a hospital without the presence of these signs. Those patients with underlying lung disease should receive more stringent monitoring in the hospital.

Respiratory distress syndrome is a disorder characterised by a failure of the lungs to produce adequate amounts of oxygen to support normal metabolic functions of the body. The condition is a life threatening emergency that can be life-threatening also for neonates, and is associated with a mortality rate of at least 50%. Survival can be improved when appropriate treatment is delivered in a timely fashion. There is no cure for respiratory distress syndrome. Instead there are a number of treatments that can improve outcomes or the quality of life of the sufferer. If respiratory distress syndrome is not treated in a hospital it can lead to death.

Aspiration of gastric contents or aspiration of fluids in the tracheobronchial tree lead to laryngeal edema, hyperinflation and respiratory failure which result from impaired gas exchange and are the main factors in the aetiology of RDS.

Around 100,000 new cases of RDS occur annually in the United States, though this accounts for only 10% of all new cases of respiratory distress.

Treatment of infant respiratory distress syndrome depends on the degree and progress of the lung disease. However, ventilation, high flow oxygen, and antibiotics are often prescribed. Airway control includes continuous positive airway pressure or intubation with mechanical ventilation. The use of corticosteroids, antihistamines, and bronchodilators is common.\n

The current paradigm of managing neonates and children with severe RDS has been modified. New diagnostic and treatment methods have made it possible to reduce the incidence of RDS by over 50%.

The lung has three major types of cells: epithelial cells, vascular endothelial cells, and mesenchymal stroma, and these cells can be induced to differentiate into pulmonary epithelial cells. The MSCs isolated from the lung tissue of the pulmonary emphysema patients displayed strong adhesion to the fibroblast sheets by their adhesion molecules, suggesting that they are capable of adhering to fibroblast sheets and migrating by means of their adhesion molecules.

Patients with a postnatal diagnosis of RDS who had a normal BMI at birth typically have similar oxygenation levels to those of non-RDS patients at baseline. This suggests that high adipose stores are not a sufficient cause of hypoxia in RDS. In addition, we found that patients who began developing RDS after 35 weeks had significantly higher baseline O(2) values than patients in whom RDS developed before 35 weeks, suggesting that O(2) may be a more sensitive parameter than BMI for predicting RDS severity.

Recent advances in this field are encouraging. In spite of the limited number of reported studies, it seems that a number of clinical trials and large-scale-controlled studies are underway. Nevertheless, further research on the mechanisms underlying some of these preclinical results will be necessary to clarify the optimal clinical conditions for the use of hMSCs as a therapeutic tool.

Findings from a recent study shows that combinations of MSC-based treatments result in better treatment options than the use of MSCs alone, supporting the rationale for combination therapy with other types of stem cell treatments in the clinic.

In a single arm non-randomized, placebo-controlled phase 2 study, hMSC-collagens was associated with improvements in the quality of life of patients with severe RDS, compared to placebo. hMSC-collagens, is an orphan drug approved for clinical trials by the US FDA on 12 November 2013. It is manufactured by Genentech and is the first cell-based product to enter the market for the treatment of chronic lung diseases.