Table 1.
MSCs-derived secretome (e.g., exosome) therapy in preclinical models of acute neurodegeneration
| Condition | Model | Cell source | Administration route | Results | Ref. |
|---|---|---|---|---|---|
| SCI | Mice | BM | Intravenous | Stimulating functional behavioral restoration via improving M2/M1 macrophage ratio by exosomal miR-216a-5p | [120] |
| SCI | Rat | AM | Intravenous | Reducing inflammation and eliciting antioxidant effects through MSC-derived exosomes immobilized in hydrogel | [138] |
| SCI | Rat | UC | Intrathecal | Plummeting pro-inflammatory cytokine TNF-α and IL-1β, while improving IL-10, BDNF, and GDNF levels in brain tissue | [164] |
| SCI | Rat | BM | Intravenous | Alleviating neurological damage through suppressing Ern1 and promoting M2 macrophage by exosomal microRNA-124-3p | [165] |
| SCI | Rat | BM | Intravenous | Repairing spinal cord injury by exosomal miRNA-29b | [166] |
| SCI | Rat | BM | Intravenous | Repairing spinal cord injury by inhibition of A1 neurotoxic reactive astrocytes activation | [117] |
| SCI | Rat | UC | Intrathecal | Reducing the c-Fos, GFAP, Iba1, TNF-α, and IL-1β, and improving IL-10 and GDNF levels | [137] |
| SCI | Rat | BM | Intravenous | Inhibition of pericytes migration and improving the BSCB integrity by targeting NF-κB p65 signaling in pericytes | [133] |
| SCI | Mice | BM | Intraspinal | Promoting angiogenesis and axon growth leading to the functional rescue | [167] |
| SCI | Rat | BM | Intravenous | Promoting the neurogenesis and angiogenesis, while reducing apoptosis by exosomal miR-126 | [128] |
| SCI | Rat | BM | Intravenous | Hindrance of complement activation | [168] |
| SCI | Mice | Placental | Intrathecal | Potentiating angiogenesis leading to the ameliorated neurologic function | [129] |
| SCI | Rat | BM | Intravenous | Improving M2 macrophage polarization | [121] |
| SCI | Rat | UC | Intravenous | Exerting anti-inflammatory and anti-fibrotic action | [169] |
| SCI | Rat | NA | Intravenous | Attenuation of inflammation through down-regulation of TLR4/NF-κB signaling pathway by exosomal miR-145-5p | [170] |
| SCI | Rat | BM | Intravenous | Inhibition of A1 neurotoxic reactive astrocytes activation in part via suppressing NF-κB translocation | [118] |
| TBI | Rat | BM | Intravenous | Promoting functional recovery through triggering endogenous angiogenesis and neurogenesis and also down-regulation of neuroinflammation | [104] |
| TBI | Rat | AT | Intracerebroventricular | Reducing microglia activation | [145] |
| TBI | Rat | BM | Intravenous | Amelioration of sensorimotor and cognitive dysfunction, attenuation of hippocampal neuronal cell loss, inducing the angiogenesis and neurogenesis, and mitigation of neuroinflammation | [143] |
| TBI | Rat | BM | Intranasal | Exosome efficient migration to the injured Forebrain | [171] |
| TBI | Rat | BM | Intravenous | Amelioration of neurological functions, decreasing brain edema through favoring BBB integrity | [23] |
| TBI | Swine | BM | Intravenous | Boosting neural plasticity along with reducing inflammation and apoptosis ensuring reduced brain lesion zone | [147] |
| TBI | Mice | BM | Intraorbital | Mitigation of early inflammatory responses | [144] |
| TBI | Rat | BM | Intravenous | Triggering endogenous angiogenesis and neurogenesis | [142] |
| TBI | Swine | BM | Intravenous | Induction of neuroprotection and supporting BBB integrity | [90] |
| TBI | Rat | BM | Intravenous | Stimulating neuroprotection via exosomal miR-216a-5p, which up-regulates BDNF expression | [172] |
| TBI | Mice | BM | Intravenous | Amelioration of cognitive deficits | [173] |
| Stroke | Mice | AT | Intravenous | Reducing autophagy by exosomal miR-25 | [174] |
| Stroke | Rat | BM | Intravenous | Stimulation of neuritis outgrowth by exosomal miR-133b | [163] |
| Stroke | Mice | BM | Intravenous | Obstruction of neuroinflammation and averting cerebral infarction by exosomal miR-542-3p | [175] |
| Stroke | Mice | UC | Intravenous | Attenuation of microglial-mediated neuroinflammation through down-regulation of the IRAK1/TRAF6 signaling axis by exosomal miR-146a-5p | [159] |
| Stroke | Rat | BM | Intravenous | Promoting the neurorestorative effects | [176] |
| Stroke | Rat | BM | Intravenous | Suppression of the neuronal apoptosis and M1 macrophage polarization by exosomal miR-146a-5p causes alleviated intracerebral hemorrhage | [177] |
| Stroke | Mice | BM | Intravenous | Induction of neuroprotection | [178] |
| Stroke | Rat | BM | Intravenous | Improving the functional recovery and neurovascular plasticity | [179] |
| Stroke | Rat | UCB | Intravenous | Triggering the functional recovery | [180] |
| Stroke | Rat | AT | Intravenous | Attenuation of the ischemic brain injuries by targeting miR-21-3p/MAT2B axis | [181] |
| Stroke | Rat | BM | Intravenous | Promoting the axon–myelin remodeling by exosomal miR-17-92 | [182] |
| Stroke | Mice | BM | Intravenous | Reducing inflammation, pathological alterations and apoptosis by exosomal miR-221-3p | [183] |
MSCs mesenchymal stromal cells, TBI traumatic brain injury, SCI spinal cord injury, AT adipose tissue, BM bone marrow, UCB umbilical cord (UC) blood, miRNAs microRNAs, IL interleukin, TNFα tumor necrosis factor α, BSCB blood–spinal cord barrier, GDNF glial cell-derived neurotrophic factor, NF-κB nuclear factor kappa B, TLRs toll-like receptors, BBB blood–brain barrier, TRAF6 TNF receptor-associated factor 6, IRAK1 interleukin 1 receptor-associated kinase 1, BDNF brain-derived neurotrophic factor, NA not applicable