Identifying Immunomodulatory Subpopulations of Adipose Stromal Vascular Fraction and Stem/Stromal Cells Through Single-Cell Transcriptomics and Bulk Proteomics.

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)

A primary therapeutic characteristic of mesenchymal stem/stromal cells (MSCs) is their immunomodulatory activity. Adipose-derived stem/stromal cells (ASCs) are an abundant and easily isolated source of MSCs shown to have high immunosuppressive activity, making them attractive for therapy. Understanding the heterogeneous immunomodulatory potential of ASCs within the stromal vascular fraction (SVF) of adipose tissue could better inform treatment strategies. In this study, we integrate single-cell RNA sequencing (scRNA seq) with bulk proteomics to characterize subpopulations of SVF-derived ASCs that are phenotypically similar to cytokine-licensed, cultured ASCs. To better define the licensing process, we present scRNA seq and bulk proteomics data of cultured (P2) ASCs exposed to inflammatory cytokines, showing enrichment of pathways related to inflammation and apoptosis that positively correlate to the cytokine-mediated, trajectory-derived pseudotime. Using the Scissor algorithm, we integrate the proteomics data with uncultured (P0) SVF scRNA seq data, identifying an ASC subpopulation that is phenotypically like the cytokine-stimulated ASCs (Scissor-positive). Interactome analysis identifies Scissor-positive ASCs as stress adaptive immune regulators that function through IL6 and broad SEMA4 interactions and higher Visfatin signaling, while Scissor-negative ASCs show strong signatu

Evidence level

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

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