The Influence of Cyanidin-3-Glucoside on the Modulation of Immune Cell Responses by Mesenchymal Stem Cell-Conditioned Medium

Author(s)

de Freitas, Sumara ; Makiyama, Edson Naoto ; Neves, Bruna Roberta Oliveira ; Pizzolato Cezar, Iolanda Silva Rafael ; Goncalves, Carlos Eduardo da Silva ; Rogero, Marcelo Macedo ; Fock, Ricardo Ambrosio

• Document type: Journal article
• Source: Cell Biochemistry and Function; v. 43, n. 2, p. 11-pg., 2025-02-01.

Abstract

Mesenchymal stem cells (MSCs) are emerging as promising therapeutic agents due to their immunomodulatory effects, primarily mediated via paracrine signaling. Similarly, anthocyanins, such as cyanidin-3-glucoside (C3G), have demonstrated significant anti-inflammatory properties. In this context, this study investigated the immunomodulatory potential of C3G on MSCs, and subsequent effects on macrophage and lymphocyte responses. Cytotoxicity assays identified 50 mu M as the highest nontoxic C3G concentration for MSCs. Flow cytometry confirmed that C3G treatment did not affect MSC viability or cell cycle distribution, even under LPS stimulation. Cytokine production by MSCs was evaluated after treatment with C3G and LPS. While no significant changes were observed in IL-6, IL-10, TGF-beta, or PGE2 levels, IL-1 beta production was significantly reduced in LPS-stimulated MSCs treated with C3G. Protein expression analysis revealed decreased NF kappa B phosphorylation in LPS-stimulated MSCs treated with C3G, with no changes detected in STAT-3 or PCNA expression. The immunomodulatory effects of MSC-derived conditioned media on macrophages and lymphocytes were also assessed. In LPS-stimulated macrophages, conditioned media from MSCs reduced the production of IL-1 beta, IL-6, and IL-12. Interestingly, conditioned media from C3G-treated MSCs specifically decreased TNF-alpha levels, enhanced IL-10 secretion, and further inhibited NF kappa B phosphorylation. In LPS-stimulated lymphocytes, conditioned media from C3G-treated MSCs suppressed IL-2 production while increasing IL-10 levels. In summary, these findings demonstrate that conditioned media from C3G-treated MSCs modulates immune cell responses more effectively than C3G alone. C3G influences the paracrine activity of MSCs, resulting in a shift in the secretory profile and subsequent effects on immune cell behavior. (AU)

• FAPESP's process: 21/08658-1 - Influence of protein malnutrition in the elderly on the immunomodulatory aspects of mesenchymal stromal cells and their action in the regulation of hematopoiesis
• Grantee: Ricardo Ambrósio Fock
• Support Opportunities: Regular Research Grants