Abstract
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.
Highlights
Extracellular vesicles (EVs) comprise a heterogeneous population of nano- and micro-sized vesicles secreted by virtually all cell types studied so far (Yáñez-Mó et al, 2015; Mateescu et al, 2017)
Since non-coding RNAs (ncRNAs) are expressed endogenously and regulate several cellular process through orchestrating gene expression organization of cells in cis; the secretion of ncRNAs via EVs could be envisaged for the purpose that cells might have evolved mechanism of trans-regulation between cells (Fatima and Nawaz, 2017c)
Keeping in view the proposition that ncRNAs exhibit heterogeneous regulatory mechanisms; it would be essential to determine the functional readouts arising from ncRNA regulatory effects in injured tissues
Summary
Extracellular vesicles (EVs) comprise a heterogeneous population of nano- and micro-sized vesicles secreted by virtually all cell types studied so far (Yáñez-Mó et al, 2015; Mateescu et al, 2017). MSC-derived EVs transfer anti-apoptotic miRNAs to injured cells, which promote cell survival but may elicit transcriptional modulation of target genes in injured renal epithelial cells as noticed in in-vitro as wells in-vivo models of kidney injury (Lindoso et al, 2014; Cantaluppi et al, 2015).
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