Therapies with CCL25 require controlled release via microparticles to avoid strong inflammatory reactions

Area of Science:

• Immunology
• Biomaterials Science
• Regenerative Medicine

Background:

• C-C motif chemokine ligand 25 (CCL25) is explored for treating articular cartilage degeneration via chemokine therapy.
• Poly (lactic-co-glycolic acid) (PLGA) microparticles are developed for sustained intra-articular delivery of CCL25.
• CCL25's role in immune regulation necessitates thorough assessment of its immune activation potential.

Purpose of the Study:

• To evaluate immune cell subset reactions to varying CCL25 dosages.
• To compare immune responses to directly applied CCL25 versus CCL25 released from PLGA particles.

Main Methods:

• Immune cell subsets were stimulated with CCL25 and PLGA microparticle supernatants for up to 5 days.
• Analysis included cytokine secretion, surface marker expression, polarization, and migration.
• C-C chemokine receptor type 9 (CCR9) expression was assessed on immune cells.

Main Results:

• Direct CCL25 stimulation at high doses increased inflammatory cytokines (MCP-1, IL-8, IL-1β, TNF-α, IFN-γ) and immune cell migration.
• High-dose CCL25 upregulated HLA-DR on monocytes and CD4+ T-cells.
• PLGA microparticle supernatants induced moderate cytokine increases without affecting surface markers or migration.

Conclusions:

• Direct CCL25 application can induce significant inflammatory activation of human leukocytes.
• PLGA microparticle-released CCL25 showed a reduced inflammatory profile.
• Safe and reliable delivery systems are crucial to prevent adverse inflammatory reactions in CCL25-based therapies.