Mesenchymal Stem/Stromal Cells in Asthma Therapy: Mechanisms and Strategies for Enhancement

Asthma is a complex and heterogeneous disease characterized by chronic airway inflammation, airway hyperresponsiveness, and airway remodeling. Most asthmatic patients are well-established using standard treatment strategies and advanced biologicals. However, a small group of patients who do not respond to biological treatments or are not effectively controlled by available treatment strategies remain a clinical challenge. Therefore, new therapies are urgently needed for poorly controlled asthma. Mesenchymal stem/stromal cells (MSCs) have shown therapeutic potential in relieving airway inflammation and repairing impaired immune balance in preclinical trials owing to their immunomodulatory abilities. Noteworthy, MSCs exerted a therapeutic effect on steroid-resistant asthma with rare side effects in asthmatic models. Nevertheless, adverse factors such as limited obtained number, nutrient and oxygen deprivation in vitro, and cell senescence or apoptosis affected the survival rate and homing efficiency of MSCs, thus limiting the efficacy of MSCs in asthma. In this review, we elaborate on the roles and underlying mechanisms of MSCs in the treatment of asthma from the perspective of their source, immunogenicity, homing, differentiation, and immunomodulatory capacity and summarize strategies to improve their therapeutic effect.