Extracellular vesicles from glycolytic mesenchymal stromal cells restrain arthritis progression via IL-10-Producing T and B cells.

Authors

Eliana Lara-Barba, Raúl Lagos, Yesenia Flores-Elías, Yeimi Herrera-Luna, Noymar Luque-Campos, María Jesús Araya-Sapag, Constanza Aros-Valdivia, Felipe A Bustamante-Barrientos, Liliana Yantén-Fuentes, Consuelo Covarruvias-Segovia, Consuelo Contreras, María Ignacia Cádiz, César Merino-Flores, Grégory Collin, Yessia Hidalgo-Fadic, Aliosha I Figueroa-Valdés, Hugo Tobar, Francisca Alcayaga-Miranda, María Paz Hernandez, Gino Nardocci, Estefanía Nova-Lamperti, Karine Toupet, Carolina Pradenas-Fuenzalida, Claudia Terraza, Francisca Uribe, Andrés Villarroel, Jasna V Campos, Marcela Mondaca, Pablo Cruz, Andrea Matamoros, Alvaro A Elorza, Claudio Carril, Carlos Farkas, Karina Oyarce, Andy J Pérez, Ana María Vega-Letter, Roberto Elizondo-Vega, Farida Djouad, Patricia Luz-Crawford

Published in

Theranostics. Volume 16. Issue 12. Pages 6713-6731. Epub May 11, 2026.

Abstract

Mesenchymal stromal cells (MSCs) exert potent immunomodulatory effects largely mediated by extracellular vesicles (EVs). We previously demonstrated that glycolytic reprogramming enhances the immunosuppressive capacity of human umbilical cord-derived MSCs (UC-MSCs). Here, we investigated whether this enhanced activity is transmitted through EVs and explored the contribution of EV-associated microRNAs.
EVs from naïve and glycolytically reprogrammed UC-MSCs (EVs-UC-MSC_naive and EVs-UC-MSC_glyco) were isolated, characterized, and tested for their effects on memory CD4⁺ T and B cells in vitro and their therapeutic efficacy in vivo in the delayed-type hypersensitivity (DTH) and in the collagen induced arthrtis (CIA) murine model.
EVs-UC-MSC_glyco more effectively suppressed inflammatory T cell responses, promoted IL-10-producing Tr1 and B cells, and enhanced B cell survival compared with EVs-UC-MSC_naive. In vivo, EVs-UC-MSC_glyco significantly reduced inflammation in a DTH murine model and decreased arthritis incidence and clinical severity in CIA. These effects were associated with increased Treg/Th1, Treg/Th17, Tr1/Th1, and Tr1/Th17 ratios, together with enhanced IL-10 production. MicroRNA profiling revealed enrichment of regulatory miRNAs, including miR-365a-5p, linked to suppression of pro-inflammatory signaling and activation of the IL-10 regulatory axis.
Glycolytic reprogramming enhances the therapeutic potential of UC-MSC-derived EVs, highlighting EVs-UC-MSC_glyco as promising immunomodulatory candidates for the treatment of autoimmune diseases such as arthritis.

PMID:
42244992
Bibliographic data and abstract were imported from PubMed on 13 Sep 2026.

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