N-cadherin-mimetic 3D hydrogels program pro-regenerative and immunomodulatory states in human adipose-derived mesenchymal stem cells.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Mesenchymal stromal cell (MSC) therapies critically depend on culture systems that preserve stem cell identity while appropriately configuring immunomodulatory functions. Here, we investigated how a biomimetic three-dimensional (3D) hydrogel that presents the N-cadherin-derived HAVDI motif shapes the phenotype and inflammatory programming of human adipose-derived MSCs (ADMSCs). Self-assembled HAVDI-functionalized peptide amphiphile hydrogels formed nanofibrous, mechanically stable networks that supported high cell viability and sustained encapsulation. Across all conditions-including tissue culture plastic, micromass aggregates, and 2D/3D peptide formulations-flow cytometry showed that ADMSCs remained > 90% positive for canonical MSC markers CD73, CD90, and CD105, indicating global preservation of MSC surface phenotype, with peptide-modified environments modestly stabilizing marker expression relative to uncoated plastic. In 3D HAVDI hydrogels, gene expression profiling revealed robust upregulation of p120-catenin and β-catenin, together with increased transcription of matrix-remodeling and angiogenesis-related genes (MMP2, PLAU, VEGFR2), consistent with a pro-regenerative program. Notably, 3D HAVDI cultures displayed markedly elevated basal expression of multiple immunoregulatory cytokine genes (IL-1α, IL-1β, IL-8, IFN-γ, TNF-α, GM-CSF) under LPS-negative conditions, followed

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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