Extracellular vesicles (EVs) derived from mesenchymal stromal cells (MSCs) possess pro-regenerative potential in different animal models with renal injury. EVs contain different molecules, including proteins, lipids and nucleic acids. Among the shuttled molecules, miRNAs have a relevant role in the pro-regenerative effects of EVs and are a promising target for therapeutic interventions. The aim of this study was to increase the content of specific miRNAs in EVs that are known to be involved in the pro-regenerative effect of EVs, and to assess the capacity of modified EVs to contribute to renal regeneration in in vivo models with acute kidney injuries. To this purpose, MSCs were transiently transfected with specific miRNA mimics by electroporation. Molecular analyses showed that, after transfection, MSCs and derived EVs were efficiently enriched in the selected miRNAs. In vitro and in vivo experiments indicated that EVs engineered with miRNAs maintained their pro-regenerative effects. Of relevance, engineered EVs were more effective than EVs derived from naïve MSCs when used at suboptimal doses. This suggests the potential use of a low amount of EVs (82.5 × 10) to obtain the renal regenerative effect.
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http://dx.doi.org/10.3390/ijms20102381 | DOI Listing |
Mol Biol Rep
January 2025
Medical Sociology and Psychobiology, Department of Health and Physical Activity, University of Potsdam, 14469, Potsdam, Germany.
Background: Depression constitutes a risk factor for osteoporosis, but underlying molecular and cellular mechanisms are not fully understood. MiRNAs influence gene expression and are carried by extracellular vesicles (EV), affecting cell-cell communication.
Aims: (1) Identify the difference in miRNA expression between depressed patients and healthy controls; (2) Analyze associations of these miRNAs with bone turnover markers; (3) Analyze target genes of differentially regulated miRNAs and predict associated pathways regarding depression and bone metabolism.
ACS Nano
January 2025
Department of Cancer Biology and Metastasis Research Center, University of Texas MD Anderson Cancer Center, Houston, Texas 77054, United States.
Extracellular vesicles (EVs) are generated in all cells. Systemic administration of allogenic EVs derived from epithelial and mesenchymal cells has been shown to be safe, despite carrying an array of functional molecules, including thousands of proteins. To address whether epithelial cell-derived EVs can be modified to acquire the capacity to induce an immune response, we engineered 293T EVs to harbor the immunomodulatory molecules CD80, OX40L, and PD-L1.
View Article and Find Full Text PDFACS Nano
January 2025
Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, Texas 77054, United States.
Extracellular vesicles (EVs) are cell derived nanovesicles which are implicated in both physiological and pathological intercellular communication, including the initiation, progression, and metastasis of cancer. The exchange of biomolecules between stromal cells and cancer cells via EVs can provide a window to monitor cancer development in real time for better diagnostic and interventional strategies. In addition, the process of secretion and internalization of EVs by stromal and cancer cells in the tumor microenvironment (TME) can be exploited for delivering therapeutics.
View Article and Find Full Text PDFGlobally, an estimated 2.1 billion malaria cases and 11.7 million malaria deaths were averted in the period 2000-2022.
View Article and Find Full Text PDFJ Extracell Vesicles
January 2025
Vascular Biology Program, Boston Children's Hospital, Boston, Massachusetts, USA.
Extracellular vesicles (EVs) from brain-seeking breast cancer cells (Br-EVs) breach the blood-brain barrier (BBB) via transcytosis and promote brain metastasis. Here, we defined the mechanisms by which Br-EVs modulate brain endothelial cell (BEC) dynamics to facilitate their BBB transcytosis. BEC treated with Br-EVs show significant downregulation of Rab11fip2, known to promote vesicle recycling to the plasma membrane and significant upregulation of Rab11fip3 and Rab11fip5, which support structural stability of the endosomal compartment and facilitate vesicle recycling and transcytosis, respectively.
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