ArticleRegenerative therapy2025
IFNγ and TNFα optimize salivary gland mesenchymal stromal cells: an alternative to marrow- and adipose-MSCs for radiation xerostomia.
Article in Regenerative therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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13 authors.
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Abstract
Objectives: Local mesenchymal stromal cell (MSC) administration is a promising therapy for xerostomia. MSCs deploy their advantageous effects through their trophic secretome and immunomodulatory capabilities. These functions are enhanced with IFNγ pre-licensing, but the effects of TNFα pre-licensing are unknown. Our objective was to compare MSCs by tissue source (MSC(BM), MSC(AD), and salivary gland-derived [MSC(SG)]) and by cytokine pre-licensing conditions. Methods: We used single cell and bulk RNA sequencing and ELISA to determine key trophic and immunomodulatory features differing between human MSC(BM), MSC(AD), and MSC(SG). We used ELISA and flow cytometry of T-cell co-culture to define the effect of IFNγ and/or TNFα on MSC trophic secretome and immunomodulatory capacity. Finally, we studied salivary flow and glandular recovery with MSC injection in radiation-induced xerostomia mice. Results: Bulk RNA sequencing (RNAseq) of MSC(BM), MSC(AD), and MSC(SG) revealed that they shared 85 % of transcripts. Key differences included extracellular matrix production and response to cytokines in MSC(SG). Single cell RNA sequencing showed MSC(SG) treated with IFNγ and TNFα transcriptionally diverged from other treatment conditions. Regardless of MSC source, dual stimulation of MSCs with IFNγ and TNFα produced an average of more than a 20-fold increase in R-Spondin 3 compared to vehicle conditions. Additionally, IFNγ and TNFα pre-licensing optimized immunomodulatory marker expression more than IFNγ alone. Intercellular adhesion molecule 1 increased 12-fold more, programmed death ligand 1 increased 1.4-fold more, and indoleamine 2,3 dioxygenase increased 2-fold more with IFNγ/TNFα pre-licensing than IFNγ alone. Both cytokine stimulation conditions resulted in a 1.2-fold decrease in T-cell proliferation. Gland structure, aquaporin 5, and salivary flow are preserved in irradiated mice treated with MSC(SG) pre-licensed with IFNγ/TNFα. Conclusion: MSC(SG) pre-licensed with both IFNγ and TNFα deploy advantageous functional cell attributes for salivary gland regenerative medicine.
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