Safety and efficacy of mesenchymal stromal cells mitochondria transplantation as a cell-free therapy for osteoarthritis

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dc.coverageDOI: 10.1186/s12967-024-05945-7
dc.creatorVega-Letter, Ana Maria
dc.creatorGarcía-Guerrero, Cynthia
dc.creatorYantén-Fuentes, Liliana
dc.creatorPradenas, Carolina
dc.creatorHerrera-Luna, Yeimi
dc.creatorLara-Barba, Eliana
dc.creatorBustamante-Barrientos, Felipe A.
dc.creatorRojas, Masyelly
dc.creatorAraya, María Jesús
dc.creatorJeraldo, Nicole
dc.creatorAros, Constanza
dc.creatorTroncoso, Francisca
dc.creatorPoblete, Daniela
dc.creatorCourt, Angela
dc.creatorOrtloff, Alexander
dc.creatorBarraza, Jose
dc.creatorVelarde, Francesca
dc.creatorFarkas, Carlos
dc.creatorCarril, Claudio
dc.creatorLuque-Campos, Noymar
dc.creatorAlmarza, Gonzalo
dc.creatorBarahona, Maximiliano
dc.creatorMatas, Jose
dc.creatorCereceda, Lucas
dc.creatorLorca, Rocío
dc.creatorToledo, Jorge
dc.creatorOyarce, Karina
dc.creatorVernal, Rolando
dc.creatorCaicedo, Andrés
dc.creatordel Campo, Andrea
dc.creatorHidalgo, Yessia
dc.creatorElizondo-Vega, Roberto
dc.creatorDjouad, Farida
dc.creatorKhoury, Maroun
dc.creatorFigueroa, Fernando E.
dc.creatorLuz-Crawford, Patricia
dc.date2025
dc.date.accessioned2025-11-18T19:44:06Z
dc.date.available2025-11-18T19:44:06Z
dc.description<p>Objective: The inflammatory responses from synovial fibroblasts and macrophages and the mitochondrial dysfunction in chondrocytes lead to oxidative stress, disrupt extracellular matrix (ECM) homeostasis, and accelerate the deterioration process of articular cartilage in osteoarthritis (OA). In recent years, it has been proposed that mesenchymal stromal cells (MSC) transfer their functional mitochondria to damaged cells in response to cellular stress, becoming one of the mechanisms underpinning their therapeutic effects. Therefore, we hypothesize that a novel cell-free treatment for OA could involve direct mitochondria transplantation, restoring both cellular and mitochondrial homeostasis. Methods: Mitochondria were isolated from Umbilical Cord (UC)-MSC (Mito-MSC) and characterized based on their morphology, phenotype, functions, and their ability to be internalized by different articular cells. Furthermore, the transcriptional changes following mitochondrial uptake by chondrocytes were evaluated using an Affymetrix analysis, Lastly, the dose dependence therapeutic efficacy, biodistribution and immunogenicity of Mito-MSC were assessed in vivo, through an intra-articular injection in male C57BL6 mice in a collagenase-induced OA (CIOA) model. Results: Our findings demonstrate the functional integrity of Mito-MSC and their ability to be efficiently transferred into chondrocytes, synovial macrophages, and synovial fibroblasts. Moreover, the transcriptomic analysis showed the upregulation of genes involved in stress such as DNA reparative machinery and inflammatory antiviral responses. Finally, Mito-MSC transplantation yielded significant reductions in joint mineralization, a hallmark of OA progression, as well as improvements in OA-related histological signs, with the lower dose exhibiting better therapeutic efficacy. Furthermore, Mito-MSC was detected within the knee joint for up to 24 h post-injection without eliciting an inflammatory response in CIOA mice. Conclusion: Collectively, our results reveal that mitochondria derived from MSC are transferred to key articular cells and are retained in the joint without generating an inflammatory immune response mitigating articular cartilage degradation in OA, probably through a restorative effect triggered by the stress antiviral response within OA chondrocytes.</p>eng
dc.identifierhttps://investigadores.uandes.cl/en/publications/ad910b78-ccb7-472e-9ba0-be1c820eecc1
dc.identifier.urihttps://repositorio.uandes.cl/handle/uandes/53231
dc.languageeng
dc.rightsinfo:eu-repo/semantics/openAccess
dc.sourcevol.23 (2025) nr.1
dc.subjectBiodistribution
dc.subjectImmuno-safety
dc.subjectMesenchymal stromal cells
dc.subjectMitochondria transplantation
dc.subjectMurine OA model
dc.subjectOsteoarthritis
dc.titleSafety and efficacy of mesenchymal stromal cells mitochondria transplantation as a cell-free therapy for osteoarthritiseng
dc.typeArticleeng
dc.typeArtículospa
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