Schwann cell‐derived exosomes: Janus‐faced mediators of regeneration and disease

Abstract

The phenotypic plasticity of Schwann cells (SCs) has contributed to the regenerative potential of the peripheral nervous system (PNS), but also pathological processes. This doublesided effect has led to an increasing attention to the role of extracellular vesicles (EVs) or exosomes in SCs to examine the intercellular communication between SCs and their surroundings. Here, we first describe the current knowledge of SC and EV biology, which forms the basis for the updates on advances in SC-derived exosomes research. We seek to explore in-depth the exosome-mediated molecular mechanisms involved in the regulation of SCs and their microenvironment. This review concludes with potential applications of SC-derived exosomes as delivery vehicles for therapeutics and biomarkers. The goal of this review is to emphasize the crucial role of SC-derived exosomes in the functional integration of the PNS, highlighting an emerging area in which there is much to explore and re-explore.

Role of Extracellular Vesicles in Glia-Neuron Intercellular Communication

“…Schwann cells-derived EVs (SDEVs) are also secreted from different phenotypic SCs and carry distinct protein and nucleic acid cargoes that exert either a neuroprotective or a pathological effect on the recipient cells ( Wong et al, 2022 ). In addition to the classical mechanism of axonal communication of SCs, SDEVs mediate the lateral molecular cargo transfer from SCs to axons ( Court et al, 2008 ; Lopez-Verrilli et al, 2013 ; López-Leal et al, 2020 ).…”

Exosomes as Neurological Nanosized Machines

“…33 SCs are remarkably plastic, allowing them to react in different situations to preserve the integrity of peripheral nerves. 34 Figure 2 demonstrates the delivery of exosomal miRNA-21 from repair Schwann cells improved axonal growth by down-regulation of the PTEN pathway and activation of PI3K in neurons, whereas dysfunctional repair of SC-derived exosomes prevents axonal growth and diminishes nerve conduction velocity. 34 Studies suggested that electrical stimulation (ES) therapy may delay muscle atrophy in patients with hemiplegia and promote neurological function recovery and may benefit patients with diseases causing damage to the peripheral nervous system; however, the molecular mechanism is still unknown.…”

“…34 Figure 2 demonstrates the delivery of exosomal miRNA-21 from repair Schwann cells improved axonal growth by down-regulation of the PTEN pathway and activation of PI3K in neurons, whereas dysfunctional repair of SC-derived exosomes prevents axonal growth and diminishes nerve conduction velocity. 34 Studies suggested that electrical stimulation (ES) therapy may delay muscle atrophy in patients with hemiplegia and promote neurological function recovery and may benefit patients with diseases causing damage to the peripheral nervous system; however, the molecular mechanism is still unknown. Hu et al used ES to stimulate nerve cells at 100 or 200 mV/mm for 0, 0.5, 1, and 2 h. Their result showed that coculturing nerve cells with Schwann cells could change neuronal activity by increasing glutamate levels and glutamate stimulating exosome secretion from Schwann cells, and they increased dorsal root axonal regeneration neurons in vitro and in vivo after nerve injury.…”

“…34 Guillain-Barrésyndrome (GBS) is a disorder of the PNS that originates from this current notion of immunological attack, and M1-macrophage-derived exosomes have been connected with increased Th1 and Th17 immune responses. 34 Despite the fact that exosomes derived from SCs promote axonal regeneration, neuronal viability, and prevent apoptosis, many kinds of cancer are propagated by SCs, such as pancreatic cancer and melanoma. 34 Furthermore, the PNS plays a crucial role in osteogenesis, bone metabolism, and bone remodeling.…”

“…34 Despite the fact that exosomes derived from SCs promote axonal regeneration, neuronal viability, and prevent apoptosis, many kinds of cancer are propagated by SCs, such as pancreatic cancer and melanoma. 34 Furthermore, the PNS plays a crucial role in osteogenesis, bone metabolism, and bone remodeling. Wu et al utilized SCderived exosomes in a 3D-printed porous titanium alloy to enhance the efficacy of titanium alloy scaffolds in bone repair.…”