BACKGROUND: Mitochondrial transfer is becoming recognized as an important immunomodulatory mechanism used by mesenchymal stem cells (MSCs) to influence immune cells. While effects on T cells and macrophages have been documented, the influence on B cells remains unexplored. This study investigates the modulation of B lymphocyte fate by MSC-mediated mitochondrial transfer. METHODS: MSCs labelled with MitoTracker dyes or derived from mito::mKate2 transgenic mice were co-cultured with splenocytes. Flow cytometry assessed mitochondrial transfer, reactive oxygen species (ROS) levels, apoptosis and mitophagy. Glucose uptake was measured using the 2-NBDG assay. RNA sequencing analysed gene expression changes in CD19+ mitochondria recipients and nonrecipients. Pathway analysis identified affected processes. In an LPS-induced inflammation model, mito::mKate2 MSCs were administered, and B cells from different organs were analysed for mitochondrial uptake and phenotypic changes. MSC-derived mitochondria were also isolated to confirm uptake by FACS-sorted CD19+ cells. RESULTS: MSCs transferred mitochondria to CD19+ cells, though less than to other immune cells. Transfer correlated with ROS levels and mitophagy induction. Mitochondria were preferentially acquired by activated B cells, as indicated by increased CD69 expression and glycolytic activity. Bidirectional transfer occurred, with immune cells exchanging dysfunctional mitochondria for functional ones. CD19+ recipients exhibited increased viability, proliferation and altered gene expression, with upregulated cell division genes and downregulated antigen presentation genes. In vivo, mitochondrial acquisition reduced B cell activation and inflammatory cytokine production. Pre-sorted B cells also acquired isolated mitochondria, exhibiting a similar anti-inflammatory phenotype. CONCLUSIONS: These findings highlight mitochondrial trafficking as a key MSC-immune cell interaction mechanism with immunomodulatory therapeutic potential.

• Klíčová slova
• B cell, immunoregulation, mesenchymal stem cell, metabolism, mitochondria,
• MeSH
• aktivace lymfocytů MeSH
• antigeny CD19 metabolismus   MeSH
• apoptóza MeSH
• B-lymfocyty * imunologie   fyziologie   metabolismus   MeSH
• CD antigeny MeSH
• diferenciační antigeny T-lymfocytů MeSH
• kokultivační techniky MeSH
• lektiny typu C MeSH
• mezenchymální kmenové buňky * fyziologie   MeSH
• mitochondrie * metabolismus   fyziologie   MeSH
• mitofagie MeSH
• myši transgenní MeSH
• myši MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• slezina cytologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antigeny CD19 MeSH
• CD antigeny MeSH
• CD69 antigen MeSH Prohlížeč
• diferenciační antigeny T-lymfocytů MeSH
• lektiny typu C MeSH
• reaktivní formy kyslíku MeSH

Horizontal transfer of mitochondria from the tumour microenvironment to cancer cells to support proliferation and enhance tumour progression has been shown for various types of cancer in recent years. Glioblastoma, the most aggressive adult brain tumour, has proven to be no exception when it comes to dynamic intercellular mitochondrial movement, as shown in this study using an orthotopic tumour model of respiration-deficient glioblastoma cells. Although confirmed mitochondrial transfer was shown to facilitate tumour progression in glioblastoma, we decided to investigate whether the related electron transport chain recovery is necessary for tumour formation in the brain. Based on experiments using time-resolved analysis of tumour formation by glioblastoma cells depleted of their mitochondrial DNA, we conclude that functional mitochondrial respiration is essential for glioblastoma growth in vivo, because it is needed to support coenzyme Q redox cycling for de novo pyrimidine biosynthesis controlled by respiration-linked dihydroorotate dehydrogenase enzyme activity. We also demonstrate here that astrocytes are key mitochondrial donors in this model.

• MeSH
• astrocyty metabolismus   patologie   MeSH
• buněčné dýchání MeSH
• dihydroorotátdehydrogenasa MeSH
• glioblastom * patologie   metabolismus   genetika   MeSH
• lidé MeSH
• mitochondriální DNA genetika   MeSH
• mitochondrie * metabolismus   MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• nádory mozku * patologie   metabolismus   genetika   MeSH
• oxidoreduktasy působící na CH-CH vazby metabolismus   MeSH
• proliferace buněk MeSH
• transport elektronů MeSH
• ubichinon metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• dihydroorotátdehydrogenasa MeSH
• mitochondriální DNA MeSH
• oxidoreduktasy působící na CH-CH vazby MeSH
• ubichinon MeSH

Intercellular mitochondria transfer is an evolutionarily conserved process in which one cell delivers some of their mitochondria to another cell in the absence of cell division. This process has diverse functions depending on the cell types involved and physiological or disease context. Although mitochondria transfer was first shown to provide metabolic support to acceptor cells, recent studies have revealed diverse functions of mitochondria transfer, including, but not limited to, the maintenance of mitochondria quality of the donor cell and the regulation of tissue homeostasis and remodelling. Many mitochondria-transfer mechanisms have been described using a variety of names, generating confusion about mitochondria transfer biology. Furthermore, several therapeutic approaches involving mitochondria-transfer biology have emerged, including mitochondria transplantation and cellular engineering using isolated mitochondria. In this Consensus Statement, we define relevant terminology and propose a nomenclature framework to describe mitochondria transfer and transplantation as a foundation for further development by the community as this dynamic field of research continues to evolve.

• MeSH
• lidé MeSH
• mitochondrie * transplantace   metabolismus   fyziologie   MeSH
• terminologie jako téma * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• konsensus - konference MeSH
• přehledy MeSH

Horizontal mitochondrial transfer (HMT) has emerged as a novel phenomenon in cell biology, but it is unclear how this process of intercellular movement of mitochondria is regulated. A new study in PLOS Biology reports that ADP released by stressed cells is a signal that triggers HMT.

• MeSH
• adenosindifosfát * metabolismus   MeSH
• lidé MeSH
• mitochondrie * metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• komentáře MeSH
• Názvy látek
• adenosindifosfát * MeSH

Exosomes are small vesicles of endosomal origin that are released by almost all cell types, even those that are pathologically altered. Exosomes widely participate in cell-to-cell communication via transferring cargo, including nucleic acids, proteins, and other metabolites, into recipient cells. Tumour-derived exosomes (TDEs) participate in many important molecular pathways and affect various hallmarks of cancer, including fibroblasts activation, modification of the tumour microenvironment (TME), modulation of immune responses, angiogenesis promotion, setting the pre-metastatic niche, enhancing metastatic potential, and affecting therapy sensitivity and resistance. The unique exosome biogenesis, composition, nontoxicity, and ability to target specific tumour cells bring up their use as promising drug carriers and cancer biomarkers. In this review, we focus on the role of exosomes, with an emphasis on their protein cargo, in the key mechanisms promoting cancer progression. We also briefly summarise the mechanism of exosome biogenesis, its structure, protein composition, and potential as a signalling hub in both normal and pathological conditions. Video Abstract.

• Klíčová slova
• Angiogenesis, Biomarkers, Cancer, Cancer-associated fibroblasts, Cell death, Exosomal proteins, Exosomes, Extracellular vesicles, Immune evasion, Metastasis, Therapy resistance, Tumour microenvironment,
• MeSH
• exozómy * MeSH
• extracelulární vezikuly * MeSH
• lidé MeSH
• mezibuněčná komunikace MeSH
• nádorové mikroprostředí MeSH
• nádory * MeSH
• signální transdukce MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• audiovizuální média MeSH
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH