Table 5 miRNA-engineerd EVs as an advanced drug delivery system in Neurological Disorders
Therapeutic miRNA | miRNA Enrichment | Incorporation method | Source of EVs | Target | in vitro Cell Lines Utilized | in vitro Findings | in vivo Model | in vivo Findings | Source |
|---|---|---|---|---|---|---|---|---|---|
miR-194 | Endogenous | Lentiviral Infection | Murine BM-MSCs | Neurovascular endothelial cell injury | Human brain microvascular endothelial cells | Restoration of cell viability and migratory ability after oxygen–glucose deprivation/reoxygenation treatment and inhibition of ferroptosis | N/A | N/A | Li, Xu, et al. [190] |
miR-223-3p | Endogenous | Lentiviral Infection | Murine BM-MSCs | Cerebral ischemic injury | Murine BV-2 microglia cells | Promotion of M1 to M2 phenotypic conversion of microglia cells as well as modulation of inflammatory cytokine expression, indicating a shift towards an anti-inflammatory remodeling phenotype | Rat middle cerebral artery occlusion and reperfusion model | Improved neurological dysfunction and decreased infarct volume over a 28-day period | Zhao, Yangmin, et al. [191] |
miR-17-5p | Endogenous | Lipofectamine™ Transfection | Rat primary astrocytes | Hypoxic-ischemic brain damage | Immortalized H19-7 microglial cell line | Promotion of cell viability and reduced inflammation after OGD-induced damage | Neonatal rat model of hypoxic-ischemic brain damage | Treatment alleviated brain damage and coincided with high expression of miR-17-5p. Additionally increased the healing by reducing neuronal apoptosis and inflammation | Du, Lin, et al. [192] |
miR-210 | Endogenous | DharmaFECT Transfection | Human endothelial progenitor cells | Ischemia-induced neuronal damage | SH-SY5Y human neuroblastoma cells | Reduced hypoxia and reoxygenation (H/R) induced apoptosis, attenuation of intracellular reactive oxygen species levels, and increased neuroblastoma proliferation | N/A | N/A | Yerrapragada, Sri Meghana, et al. [193] |
miR-193-3b | Exogenous | Electroporation | Murine BM-MSCs | Neuroinflammation following subarachnoid hemorrhage | N/A | N/A | Murine subarachnoid hemorrhage (SAH) model | Reduced inflammatory cytokine levels, improved neurological scoring, and decreased brain edema after SAH treatment, which indicates alleviation of neurobehavioral impairments | Lai, Niansheng, et al. [194] |
miR-22 | Endogenous | HiPerfect® Transfection | Mouse Adipose-derived MSCs | Alzheimer’s disease | PC12 rat adrenal medulla cells | Inhibition of apoptosis and significantly decreased release rate of inflammatory factors | Murine APP/PS1 model | Increased nerve function and motor ability, improved survival of nerve cells, and decreased expression of inflammatory factors | Zhai, Liping, et al. [195] |
miR-26a | Endogenous | Lipofectamine™ Transfection | Human BM-MSCs | Depression | Neonatal rat hippocampal neurons | Elevated superoxide dismutase levels and inhibition of inflammatory factors in hippocampal neurons as well as increased hippocampal neuron proliferation and restriction of apoptosis | N/A | N/A | Guo, Huirong, et al. [196] |
miR-146a | Endogenous | Lipofectamine™ Transfection | Murine BM-MSCs | Diabetic peripheral neuropathy | Human dermal microvascular endothelial cells | Inhibition of inflammatory activation | Murine diabetic peripheral neuropathy model | Significantly increased intraepidermal nerve fiber density, restoration of nerve fiber diameter, increased axonal remyelination, and inhibition of inflammatory effects | Fan, Baoyan, et al. [197] |
miR-494 | Exogenous | Exo-Fect™ Transfection | Rat BM-MSCs | Spinal cord injury | Rat dorsal root ganglion cells and alveolar macrophages | Significantly increased ganglion cell viability and promotion of M2 macrophage polarization | Rat spinal cord injury model | Homing to spinal cord lesion, reduction of lesion volume, regeneration of neurofilaments, and recovery of rat behavioral function | Huang, Wei, et al. [198] |