SECUAH 2025 > Arenas-González etal 2025

dianas | Vol 14 No 1 | marzo 2025 | e202503x002

Expansion of DMSC in High-Glucose Media Enhances Immunosuppression Through Metabolic Reprogramming

Daniel Arenas González, Paz De la Torre Merino, María Jose Morán Jiménez, AI Flores

Intituto de Investigación Hospital 12 de Octubre

dani.arenas.imas12@h12o.es

X Congreso de Señalización Celular, SECUAH 2024.
XIX Simposio de Dianas Terapéuticas.
17 a 21 de marzo, 2025. Universidad de Alcalá. Alcalá de Henares, Madrid. España.

Keywords: Mesenchymal stem cell therapies; MSC; secretome; Autoimmunity; Connexin 43

Abstract

This study explores the potential of decidua-derived mesenchymal/stromal cells (DMSC) as a promising therapeutic tool for the treatment of autoimmune and inflammatory diseases, aiming to develop a standardized product that optimizes their efficacy. Mesenchymal stem cell (MSC)-based therapies have demonstrated remarkable immunomodulatory effects through the secretion of bioactive factors. However, their clinical effectiveness remains inconsistent, and the molecular mechanisms underlying their action are not yet fully understood.
In this work, we investigated the immunomodulatory capacity of DMSC expanded under different glucose concentrations and exposed to inflammatory stimuli. We have identified key differences in their paracrine activity by gene expression analysis and the quantification of immunosuppressive molecules and cytokines secreted into the extracellular medium such as IDO, PDL2, IL-10, IL-6.
Additionally, we propose a mechanism involving connexin 43 (Cx43), by which DMSC reduce oxidative phosphorylation following inflammatory stimulation, even under normoxic conditions. This mechanism suggests that Cx43-mediated interactions play a crucial role in metabolic regulation and immune response modulation.
Our findings reveal that DMSC expanded under high-glucose conditions may exhibit enhanced immunomodulatory capacity. This study not only provides deeper insights into the paracrine mechanisms of DMSC but also lays the groundwork for improving the consistency and effectiveness of stem cell-based therapies in future clinical settings.