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Front Genet. 2017 Oct 25;8:161. doi: 10.3389/fgene.2017.00161. eCollection 2017.

Non-coding RNAs in Mesenchymal Stem Cell-Derived Extracellular Vesicles: Deciphering Regulatory Roles in Stem Cell Potency, Inflammatory Resolve, and Tissue Regeneration.

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Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Department of Pathology and Forensic Medicine, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil.
Department of Biomaterials, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Faculty of Medicine, Institute for Infection Prevention and Hospital Epidemiology, Medical Centre, University of Freiburg, Freiburg, Germany.
Department of Biochemistry and Genetics, La Trobe Institute of Molecular Science, La Trobe University, Bundoora, VIC, Australia.
Department of Molecular Biotechnology and Health Sciences, University of Turin, Torino, Italy.


Extracellular vesicles (EVs) are heterogeneous populations of nano- and micro-sized vesicles secreted by various cell types. There is mounting evidence that EVs have widespread roles in transporting proteins, lipids, and nucleic acids between cells and serve as mediators of intercellular communication. EVs secreted from stem cells could function as paracrine factors, and appear to mimic and recapitulate several features of their secreting cells. EV-mediated transport of regulatory RNAs provides a novel source of trans-regulation between cells. As such, stem cells have evolved unique forms of paracrine mechanisms for recapitulating their potencies with specialized functions by transporting non-coding RNAs (ncRNAs) via EVs. This includes the dissemination of stem cell-derived EV-ncRNAs and their regulatory effects elicited in differentiation, self-renewal, pluripotency, and the induction of reparative programs. Here, we summarize and discuss the therapeutic effects of mesenchymal stem cell-derived EV-ncRNAs in the induction of intrinsic regenerative programs elicited through regulating several mechanisms. Among them, most noticeable are the EV-mediated enrichment of ncRNAs at the injury sites contributing the regulation of matrix remodeling, epithelial mesenchymal transitions, and attraction of fibroblasts. Additionally, we emphasize EV-mediated transmission of anti-inflammatory RNAs from stem cells to injury site that potentially orchestrate the resolution of the inflammatory responses and immune alleviation to better facilitate healing processes. Collectively, this knowledge indicates a high value and potential of EV-mediated RNA-based therapeutic approaches in regenerative medicine.


exosomes; extracellular vesicles; gene expression regulation; inflammatory resolve; matrix remodeling; mesenchymal stem cells; non-coding RNA; tissue repair

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