Rationale: Under current therapeutic strategies, the cure to asthma remains elusive; thus- novel approaches for treating asthma are desperately needed. Despite mesenchymal stem cells (MSCs) have recently been established as potential candidates by virtue of their immunomodulatory properties, the underlying heterogeneity of MSCs diminishes their therapeutic efficaty.
Objectives: To establish a polarizing protocol of MSCs to augment their therapeutic benefits on asthma.
Methods: Pam3CSK4, a toll-like receptor 2 ligand, was used to license mouse bone marrow-derived MSCs. The therapeutic effects of MSCs modified with Pam3CSK4 were examined using an acute ovalbumin-induced asthma murine model. The immunosuppressive mechanisms of MSCs activated by Pam3CSK4 were further investigated to validate the applications of this modification. One-way ANOVA was applied to analyze the data with more than three compared groups.
Measurements and Main Results: For ameliorating asthma, more effective MSCs were activated with a low concentration but long-term Pam3CSK4 induction prior to intravenous administration in mice in a posttreatment manner. We further demonstated that through a toll-like receptor 2/ signal transducer and activator of transcription 3/ inducible nitric oxide synthase signaling pathway, the Pam3CSK4-primed MSCs secreted more nitric oxide to increase CD4+CD25+Foxp3+ regulatory T cell induction.
Conclusions: The promising modification of MSCs might shed light on eliminating their proinflammation-prone uncertainties, and thereafter, augmenting their therapeutic effectiveness on asthmatic inflammation.