Stem Cells Derived from Human Umbilical Cord Blood Could Treat Pulmonary Arterial Hypertension
A recently published paper in Journal of Pathology and Translational Medicine entitled “Therapeutic Effects of Umbilical Cord Blood Derived Mesenchymal Stem Cell-Conditioned Medium on Pulmonary Arterial Hypertension in Rats” suggests that human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) may be useful as a cell-based therapy for pulmonary arterial hypertension (PAH).
Pulmonary arterial hypertension is a lung disease characterized by tightening of the arteries that transport blood from the heart to the lungs. This condition yields an increase in pulmonary artery pressure, right ventricular (RV) hypertrophy, and arteriolar wall remodeling. PAH is a rare disease with an incidence of 2-3 cases per million per year, with adult females being disproportionately affected compared to adult males. Signs and symptoms of PAH may develop progressively over the years, leading patients to sometimes disregard medical consultation until the disease progresses to advanced stages. Frequent symptoms include shortness of breath, fatigue, irregular heartbeat, dizziness, racing pulse, and swelling around the ankles and feet. The cause of PAH is primarily related to excess proliferation of the pulmonary artery smooth muscle cells due to genetics or factors linked to infections, medications, and others medical conditions like congenital heart disease, systemic diseases, and metabolic disorders.
PAH is treated with various medications based on phosphodiesterase type 5 inhibitors, calcium channel blockers, endothelin receptor antagonists, activators of soluble guanylate cyclase, and prostaglandins, among others. When medications fail, lung transplant surgery is an option for some patients that can effectively cure PAH, but is often associated with life-threatening complications, such as organ rejection. Though therapeutics may extend and improve quality of life of patients with PAH, the long-term prognosis is poor, as the average survival is only 2 to 3 years from diagnosis. However, recent studies suggest that human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) may lead to a new class of therapies that can effectively treat the disease.
In this study, the researchers investigated the feasibility and safety of using conditioned medium (CM) from hUCB-MSCs in a rat model with PAH to test the hypothesis that CM from these cells may lead to improved lung function. Experimentally, they prepared CM by culturing hUCB-MSCs in three-dimensional spheroids. Afterward, they infused CM or the control unconditioned culture media into a 6-week-old rat model with PAH via the tail vein. The results suggested that compared to control unconditioned media, CM infusion improved the PAH conditions in the treated rats by reducing the ventricular pressure, the right to left ventricle ratio, and respiratory function.
In summary, the researchers found that levels of enzymes that create DNA molecules expressed in immature immune cells decreased significantly in the CM treated rats. This suggests the potential therapeutic benefit of the CM in improving PAH-mediated lung tissue damage. An increase in number of the small protein useful in cell signaling and tissue inhibitor is also observed. The latter may indicate that these species play important roles in the mechanism, requiring future investigations to gain a better understanding of their functions.