4.4 Review

Exosomal microRNAs from mesenchymal stem/stromal cells: Biology and applications in neuroprotection

Journal

WORLD JOURNAL OF STEM CELLS
Volume 13, Issue 7, Pages 776-794

Publisher

BAISHIDENG PUBLISHING GROUP INC
DOI: 10.4252/wjsc.v13.i7.776

Keywords

Mesenchymal stromal cells; Mesenchymal stromal cell-derived exosomes; Exosomal microRNAs; Neuroprotective effect

Funding

  1. National Institute on Aging of the National Institutes of Health through the UC Davis Alzheimer's Disease Center Pilot Program [P30AG010129, 5R01NS10076102, 1R01NS115860-01A1]
  2. Shriners Hospitals for Children Research Grants [85108-NCA19, 85135-NCA-21]
  3. Shriners Hospitals for Children Postdoctoral Fellowship [84705-NCA-19]

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Exosomal miRNAs play a key role in the neuroprotective effects of MSCs by promoting neurogenesis, neurite remodeling, survival, and neuroplasticity, showing significant therapeutic potential for neurological disorders such as stroke, traumatic brain injury, and neuroinflammatory or neurodegenerative diseases. Various bioengineering approaches are discussed for isolating exosomes, optimizing yield, and manipulating miRNA content to enhance therapeutic potential.
Mesenchymal stem/stromal cells (MSCs) are extensively studied as cell-therapy agents for neurological diseases. Recent studies consider exosomes secreted by MSCs as important mediators for MSCs' neuroprotective functions. Exosomes transfer functional molecules including proteins, lipids, metabolites, DNAs, and coding and non-coding RNAs from MSCs to their target cells. Emerging evidence shows that exosomal microRNAs (miRNAs) play a key role in the neuroprotective properties of these exosomes by targeting several genes and regulating various biological processes. Multiple exosomal miRNAs have been identified to have neuroprotective effects by promoting neurogenesis, neurite remodeling and survival, and neuroplasticity. Thus, exosomal miRNAs have significant therapeutic potential for neurological disorders such as stroke, traumatic brain injury, and neuroinflammatory or neurodegenerative diseases and disorders. This review discusses the neuroprotective effects of selected miRNAs (miR-21, miR-17-92, miR-133, miR-138, miR-124, miR-30, miR146a, and miR-29b) and explores their mechanisms of action and applications for the treatment of various neurological disease and disorders. It also provides an overview of state-of-the-art bioengineering approaches for isolating exosomes, optimizing their yield and manipulating the miRNA content of their cargo to improve their therapeutic potential.

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