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

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dc.article.number26
dc.catalogadorvdr
dc.contributor.authorVega Letter, Ana María
dc.contributor.authorGarcía Guerrero, Cynthia
dc.contributor.authorYantén Fuentes, Liliana
dc.contributor.authorPradenas, Carolina
dc.contributor.authorHerrera Luna, Yeimi
dc.contributor.authorLara Barba, Eliana
dc.contributor.authorBustamante Barrientos, Felipe A.
dc.contributor.authorRojas, Masyelly
dc.contributor.authorAraya, María Jesús
dc.contributor.authorJeraldo, Nicole
dc.contributor.authorAros, Constanza
dc.contributor.authorTroncoso, Francisca
dc.contributor.authorPoblete, Daniela
dc.contributor.authorCourt, Angela
dc.contributor.authorOrtloff, Alexander
dc.contributor.authorBarraza, Jose
dc.contributor.authorVelarde, Francesca
dc.contributor.authorFarkas, Carlos
dc.contributor.authorAlmarza Wacquez, Gonzalo Raimundo
dc.contributor.authorCampo, Andrea del
dc.date.accessioned2025-01-14T17:39:55Z
dc.date.available2025-01-14T17:39:55Z
dc.date.issued2025
dc.date.updated2025-01-12T01:04:42Z
dc.description.abstractThe 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.
dc.fechaingreso.objetodigital2025-01-11
dc.format.extent14 páginas
dc.fuente.origenSIPA
dc.identifier.doi10.1186/s12967-024-05945-7
dc.identifier.eissn1479-5876
dc.identifier.urihttps://doi.org/10.1186/s12967-024-05945-7
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/89644
dc.information.autorucEscuela de Psicología; Almarza Wacquez, Gonzalo Raimundo; S/I; 163751
dc.information.autorucEscuela de Química; Campo, Andrea del; 0000-0003-3830-7334; 1099680
dc.language.isoen
dc.nota.accesocontenido completo
dc.pagina.final14
dc.pagina.inicio1
dc.revistaJournal of Translational Medicine
dc.rightsacceso abierto
dc.rights.licenseCC BY-NC-ND 4.0 Attribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectMitochondria transplantation
dc.subjectMesenchymal stromal cells
dc.subjectOsteoarthritis
dc.subjectMurine OA model
dc.subjectBiodistribution
dc.subjectImmuno-safety
dc.subject.ddc610
dc.subject.deweyMedicina y saludes_ES
dc.subject.ods03 Good health and well-being
dc.subject.odspa03 Salud y bienestar
dc.titleSafety and efficacy of mesenchymal stromal cells mitochondria transplantation as a cell-free therapy for osteoarthritis
dc.typeartículo
dc.volumen23
sipa.codpersvinculados163751
sipa.codpersvinculados1099680
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