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.

A Plasma Circular RNA Profile Differentiates Subjects with Alzheimer’s Disease and Mild Cognitive Impairment from Healthy Controls

“…Several of the circRNA-associated miRNAs are expressed in the brain, with relatively defined roles in brain development (miR-18a, miR-18b [ 25 , 26 ], miR-30 [ 27 , 28 ], miR-592 [ 29 , 30 ]) or adult brain (miR-18a [ 31 , 32 ], miR-149 [ 33 , 34 , 35 ], miR-30 [ 36 , 37 ], miR-21 [ 28 , 38 ], miR-592 [ 39 ]. Some of these were investigated in the field of dementias and neurodegenerative diseases.…”

The potential use of mesenchymal stem cells-derived exosomes as microRNAs delivery systems in different diseases

“…Moreover, ESCRT-autonomous pathways, including ceramide–interceded mechanisms, have been demonstrated to be implicated in load sorting into EXOs. Additional study is required to discover the particulars of the elective miRNA loading method [ 88 ]. Moreover, RBPs and cell priming (such as hypoxia and inflammatory cytokines) methods can also be used to regulate the miRNA load of EXOs.…”

“…A relationship matrix analysis investigation demonstrated a weak correlation between the RNA amount of MSC-EXOs and the principal MSCs, showing that miRNAs were electively packed into the EXOs. It has been proposed that RNA-binding proteins (RBPs), including hnRNPA2B1 and hnRNPA1 per se, connect to miRNAs and control Additional study is required to discover the particulars of the elective miRNA loading method [88]. Moreover, RBPs and cell priming (such as hypoxia and inflammatory cytokines) methods can also be used to regulate the miRNA load of EXOs.…”

Emerging Potential of Exosomal Non-coding RNA in Parkinson’s Disease: A Review

“…Studies have shown that miR-137 targeted OXR1 and negatively regulated its expression, and inhibiting miR-137 or up-regulating OXR1 can promote the vitality of neurons in PD models and minimize apoptosis, accompanied by a drop in MDA content and ROS levels and an increase in SOD levels ( Jiang et al, 2019 ). Exosomes derived from Mesenchymal Stem Cells/Somatic Cells (MSC) can transport miRNAs to neuronal cells and are critical in immunological modulation, neurite remodeling, neurogenesis, and axonal growth and CNS recovery ( Vilaca-Faria et al, 2019 ; Nasirishargh et al, 2021 ). Jiang et al injected serum-derived exosomes into PD mice, and the loss of function of miR-137 antagomir demonstrated that miR-137 down-regulation could minimize PD’s oxidative stress damage by up-regulating OXR1, reduce pole-climbing time, and increasing traction test score ( Jiang et al, 2019 ).…”