The ATP synthase inhibition induces an AMPK-dependent glycolytic switch of mesenchymal stem cells that enhances their immunotherapeutic potential

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dc.coverageDOI: 10.7150/thno.51631
dc.creatorContreras-Lopez, Rafael
dc.creatorElizondo-Vega, Roberto
dc.creatorLuque-Campos, Noymar
dc.creatorTorres, María José
dc.creatorPradenas, Carolina
dc.creatorTejedor, Gautier
dc.creatorParedes-Martínez, María José
dc.creatorVega-Letter, Ana María
dc.creatorCampos-Mora, Mauricio
dc.creatorRigual-Gonzalez, Yandi
dc.creatorOyarce, Karina
dc.creatorSalgado, Magdiel
dc.creatorJorgensen, Christian
dc.creatorKhoury, Maroun
dc.creatorGarcia-Robles, María de los Ángeles
dc.creatorAltamirano, Claudia
dc.creatorDjouad, Farida
dc.creatorLuz-Crawford, Patricia
dc.date2021
dc.date.accessioned2025-11-18T19:40:11Z
dc.date.available2025-11-18T19:40:11Z
dc.description<p>Objectives: Mesenchymal Stem/Stromal Cells (MSC) are promising therapeutic tools for inflammatory diseases due to their potent immunoregulatory capacities. Their suppressive activity mainly depends on inflammatory cues that have been recently associated with changes in MSC bioenergetic status towards a glycolytic metabolism. However, the molecular mechanisms behind this metabolic reprogramming and its impact on MSC therapeutic properties have not been investigated. Methods: Human and murine-derived MSC were metabolically reprogramed using pro-inflammatory cytokines, an inhibitor of ATP synthase (oligomycin), or 2-deoxy-D-glucose (2DG). The immunosuppressive activity of these cells was tested in vitro using co-culture experiments with pro-inflammatory T cells and in vivo with the Delayed-Type Hypersensitivity (DTH) and the Graph versus Host Disease (GVHD) murine models. Results: We found that the oligomycin-mediated pro-glycolytic switch of MSC significantly enhanced their immunosuppressive properties in vitro. Conversely, glycolysis inhibition using 2DG significantly reduced MSC immunoregulatory effects. Moreover, in vivo, MSC glycolytic reprogramming significantly increased their therapeutic benefit in the DTH and GVHD mouse models. Finally, we demonstrated that the MSC glycolytic switch effect partly depends on the activation of the AMPK signaling pathway. Conclusion: Altogether, our findings show that AMPK-dependent glycolytic reprogramming of MSC using an ATP synthase inhibitor contributes to their immunosuppressive and therapeutic functions, and suggest that pro-glycolytic drugs might be used to improve MSC-based therapy.</p>eng
dc.identifierhttps://investigadores.uandes.cl/en/publications/a2c1f802-cffc-4cdc-a1ac-129a7719c5e2
dc.identifier.urihttps://repositorio.uandes.cl/handle/uandes/51161
dc.languageeng
dc.rightsinfo:eu-repo/semantics/openAccess
dc.sourcevol.11 (2021) nr.1 p.445-460
dc.subjectAMPK activity
dc.subjectATP synthase inhibition
dc.subjectGlycolytic metabolism
dc.subjectImmunotherapy
dc.subjectMSC
dc.subjectSDG 3 - Good Health and Well-being
dc.titleThe ATP synthase inhibition induces an AMPK-dependent glycolytic switch of mesenchymal stem cells that enhances their immunotherapeutic potentialeng
dc.typeArticleeng
dc.typeArtículospa
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