PD-L1-Expressing Mesenchymal Stem Cells for Autoimmune Diseases: From Avidity-Based Microfluidic Enrichment to Enhanced Immunoregulation

초록

Mesenchymal stem cell (MSC) therapy has emerged as an effective strategy for immune-mediated disorders by modulating immune activation and inflammatory responses; however, clinical translation remains limited by intrinsic cellular heterogeneity and inconsistent immunoregulatory potency. Here, we present an avidity-based microfluidic sorting platform for high-sensitivity enrichment of MSCs with elevated programmed death-ligand 1 expression (PD-L1High MSCs) via dendrimer-mediated multivalent interactions. The platform utilizes surface-immobilized dendrimer–peptide conjugates, in which poly(amidoamine) dendrimers function as multivalent scaffolds that amplify individual peptide–receptor interactions into strong overall avidity, yielding enhanced PD-L1 binding kinetics compared with conventional antibodies. When integrated into a microfluidic system, this avidity interface enables selective capture of PD-L1High MSCs under controlled shear stress, followed by mild proteolytic dissociation for gentle recovery while preserving cell viability and proliferative capacity. Functionally, enriched PD-L1High MSCs exhibit enhanced immunosuppressive activity, characterized by reduced secretion of TNF-α and IFN-γ, reflecting effective suppression of immune effector cell activation and resulting in protection of normal epithelial cells in coculture assays. Compared with fluorescence-activated cell sorting, this platform achieves superior functional enrichment without antibody labeling or loss of cell functionality. Collectively, this study establishes an avidity-based microfluidic strategy to mitigate MSC heterogeneity and enable scalable production of immunoregulatory MSCs. © 2026 The Author(s). Small Structures published by Wiley-VCH GmbH.

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