Quantitative evaluation of mesenchymal stromal cell immunomodulatory potency and cost-effectiveness of cytokine licensing for translational application

Mesenchymal stromal cells (MSCs) possess strong immunomodulatory properties and are increasingly applied in inflammatory and immune-mediated diseases. Cytokine licensing, particularly with interferon-γ (IFN-γ), further enhances their therapeutic potential. However, standardized and quantitative approaches for evaluating MSC immunomodulatory capacity remain limited. We established a quantitative rating scale to assess the immunomodulatory capacity of MSCs and their extracellular vesicles. Using human bone marrow-derived MSC datasets, four weighting approaches, Analytic Hierarchy Process (AHP), Principal Component Analysis (PCA), the Entropy method, and the Independence method, were applied to determine the relative importance of indicators including T-cell suppression, regulatory T-cell induction, and key molecular markers. Cytokine licensing strategies were compared and paired with an economic feasibility assessment. PCA and AHP performed best for indicator prioritization, with PCA yielding balanced weight distribution and AHP providing strong discriminative ability. Entropy and Independence methods emphasized variability and independence but showed weaker differentiation. IFN-γ was identified as the most effective licensing cytokine, while dual-licensing combinations such as IFN-γ/TGF-β1 achieved the highest overall immunomodulatory scores. Economic evaluation similarly favored IFN-γ–containing strategies, particularly in combination with TGF-β1. This study proposes an integrated framework combining immunomodulatory evaluation and economic feasibility to support standardized assessment of MSC function. The findings inform optimization of cytokine licensing strategies and may guide future clinical and economic decision-making for MSC-based therapies.