Mesenchymal stem cells attenuated PLGA-induced inflammatory responses by inhibiting host DC maturation and function

Area of Science:

• Biomaterials Science
• Immunology
• Regenerative Medicine

Background:

• Poly lactic-co-glycolic acid (PLGA) scaffolds are widely used in tissue repair but often trigger significant inflammatory responses.
• Dendritic cells (DCs) play a crucial role in initiating immune responses, and PLGA can induce their maturation, potentially exacerbating inflammation.

Purpose of the Study:

• To investigate the modulatory effects of mesenchymal stem cells (MSCs) on PLGA-induced DCs (PLGA-DCs).
• To explore the potential of MSCs in mitigating PLGA-associated inflammation for improved tissue repair.

Main Methods:

• In vitro co-culture of mouse MSCs and PLGA-stimulated DCs.
• Analysis of DC maturation markers, cytokine expression, and T cell differentiation.
• In vivo studies using MSC-PLGA constructs in mice to assess DC maturation, immune cell populations, and inflammatory responses at the scaffold site.

Main Results:

• MSCs inhibited PLGA-DC maturation, dendrite formation, and pro-inflammatory factor expression.
• MSC-educated PLGA-DCs promoted Th2 and regulatory T cell differentiation while suppressing Th1 and Th17 cells.
• In vivo, MSCs reduced mature DC proportions, alleviated inflammation around PLGA scaffolds, and shifted immune cell balance towards anti-inflammatory profiles.

Conclusions:

• MSCs effectively suppress PLGA-induced DC maturation and immune responses both in vitro and in vivo.
• Targeting DCs with MSCs presents a novel therapeutic strategy to reduce inflammation and enhance the efficacy of PLGA scaffold-based tissue repair.