Surface-engineered mesenchymal stem cell for refractory asthma therapy: Reversing airway remodeling

Area of Science:

• Biomedical Engineering
• Regenerative Medicine
• Pulmonology

Background:

• Asthma involves airway remodeling via subepithelial fibrosis and vascular proliferation, leading to respiratory failure.
• Inhaled corticosteroids (ICSs) manage acute attacks but fail to prevent refractory asthma progression.
• Current treatments do not address the underlying airway remodeling in severe asthma.

Purpose of the Study:

• To develop a novel therapy for refractory asthma by reversing airway remodeling.
• To engineer mesenchymal stem cells (MSCs) with drug-loaded micelles for targeted delivery.
• To evaluate the efficacy of MSCs/PVLA in preventing fibrosis and angiogenesis.

Main Methods:

• Constructed surface-engineered MSCs (MSCs/PVLA) with reactive oxygen species-responsive polymeric micelles.
• Loaded micelles with vactosertib (VST) and linifanib (LFN) to inhibit fibrosis and angiogenesis.
• Utilized MSCs' inflammation tropism for migration to the tracheal lumen and drug release.

Main Results:

• MSCs/PVLA migrated to the inflamed tracheal lumen.
• Released VST and LFN inhibited subepithelial fibrosis and angiogenesis, key to airway remodeling.
• MSCs modulated the pathological microenvironment by reducing inflammatory cell infiltration and cytokine secretion.

Conclusions:

• MSCs/PVLA effectively reverses airway remodeling in a model of refractory asthma.
• This therapy shows potential in preventing disease exacerbations and treating severe asthma.
• Surface-engineered MSCs offer a promising strategy for refractory asthma management.