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

Abstract

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.

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

Figure 1

Neuroprotective pathways regulated by mesenchymal stem/stromal cell-derived exosomes. A: Mesenchymal stem/stromal cell-derived exosomal miR-21; B: Mesenchymal stem/stromal cell-derived exosomal miR-17-92; C: Mesenchymal stem/stromal cell-derived exosomal miR-133.

Figure 2

Mesenchymal stem/stromal cell-derived exosomes overexpressing miR-138 repressed inflammatory and pro-apoptotic factors, and increased anti-apoptotic and cell cycle markers.

Figure 3

Neuroprotective pathways regulated by exosomal microRNAs. A: Exosomal miR-124; B: Exosomal miR-146a; C: Exosomal miR-29.

Figure 4

Exosomal miR-30 regulated autophagy-mediated brain injury by promoting anti-inflammatory (M2) macrophage polarization and suppressing pro-inflammatory macrophages (M1) polarization.

Figure 5

Neuroprotective effects and therapeutic potential of mesenchymal stem/stromal cell-derived exosomal miRNAs for neurological disorder disease models.