TABLE 2.
Studies reporting the critical roles of various types of stem cell‐derived exosomes in communication between the periphery and the CNS.
| Exosome source | Substance carried | Recipient cell | Disease | Model | Outcome | Ref. |
|---|---|---|---|---|---|---|
| BMSCs | Not given | Neurons/Microglia | TBI | TBI in rats |
↑Spatial learning ↑Neurogenesis in the dentate gyrus ↓Neurological deficits ↓Foot‐fault frequency ↓Brain inflammation |
166 |
| BMSCs | MiR‐17‐92 | Neurons | TBI | CCI‐TBI in rats |
↑Sensorimotor and cognitive function ↑Angiogenesis and neurogenesis ↓Neuroinflammation ↓Hippocampal neuronal cell loss |
175 |
| BMSCs | MiR‐17‐92 | Neurons | Stroke | MCAO in rats |
↑Neurite remodeling ↑Neuronal dendritic plasticity ↑Neurogenesis and oligodendrogenesis ↑PI3K/Akt/mTOR signaling pathway ↓PTEN level |
177 |
| BMSCs | RNAs/Proteins | Neurons/Microglia |
EBI after SAH |
SAH in rats |
↑Neurological functions ↑BBB integrity ↓Brain water content ↓HMGB1‐TLR4 signaling pathway ↓Inflammation ↓Apoptosis |
178 |
| BMSCs | MiR‐124 | Cortical neural progenitors | IS | Photothrombosis in mice | ↑Neurogenesis | 182 |
| BMSCs | Not given |
Astrocytes/ Neurons |
Stroke | MCAO in rats |
↑Functional recovery ↑Axonal plasticity ↑Neurite remodeling |
183 |
| BMSCs | MiR‐132‐3p | BMECs | IS | MCAO in mice |
↑ZO‐1 and Claudin‐5 expression ↑PI3K/Akt/eNOS signaling pathway ↓Cerebral injury ↓Permeability ↓ROS production and apoptosis ↓BBB disruption |
184 |
| BMSCs | Not given |
Astrocytes/ Microglia |
AD | APP/PS1 mice |
↑Learning and memory capabilities ↑Restoration of synaptic dysfunction ↓Inflammatory responses |
185 |
| ADSCs | Not given | Microglia | Neural injury | In vitro |
↓Microglial activation ↓NF‐kB and MAPK signaling pathway ↓Cytotoxicity of activated microglia ↓Neural injury |
188 |
| hADSCs | Neprilysin | N2a cells | AD | In vitro |
↓Secreted Aβ40 and Aβ42 levels ↓Intracellular Aβ42 level |
189 , 191 |
| ADMSCs | Not given | Oligodendrocyte | Stroke | Subcortical infarct model in rats |
↑Functional recovery ↑Fiber tract integrity ↑Axonal sprouting ↑White matter repair markers ↑ White matter integrity |
192 |
| ADSCs | MiR‐126 |
Neurons/ Microglia |
Stroke | MCAO in rats |
↑Functional recovery ↑Neurogenesis ↓Neuroinflammation |
193 |
| ADSCs | MiR‐30d‐5p | Microglia | AIS | AIS in rats |
↑M2 microglia/macrophage polarization ↓Cerebral injury area of infarction ↓Autophagy |
194 |
| ADSCs | MiR‐181b‐5p | BMECs | Stroke | MCAO in rats | ↑Angiogenesis of BMECs | 195 |
| ADMSCs | MiR‐25‐3p | Neurons | Stroke | MCAO in mice |
↑Neuroprotection ↑Autophagic flux |
196 |
| ADSCs | Not given | Neurons | ALS | ALS model in vitro |
↓Mitochondrial dysfunction ↓SOD‐1 aggregation |
197 |
| hADSCs | Not given |
Microglia/ Macrophages |
TBI | TBI in rats |
↑Functional recovery ↑Neurogenesis ↓Neuroinflammation ↓Neuronal apoptosis |
176 |
| huMSCs | Not given | Microglia | Perinatal brain injury | Perinatal brain injury in rats |
↓TLR4/CD14 signaling pathway ↓Proinflammatory molecules production ↓Microgliosis |
218 |
| huMSCs | Not given | Microglia | HIBD | In vitro |
↑FOXO3a‐dependent mitophagy ↓Microglial pyroptosis |
206 |
| huMSCs | miR‐26b‐5p | PC12 cells | EBI after SAH | SAH in rats |
↓p38 MAPK/STAT3 signaling pathway ↓OxyHb‐induced cell injury |
208 |
| huMSCs | miR‐206 modified | Neurons | EBI after SAH | SAH in rats |
↑Neurological deficit ↑BDNF/TrkB/CREB signaling pathway ↓Brain edema ↓Neuronal apoptosis |
207 |
| huMSCs | Not given | Microglia | AD | AβPP/PS1 mice |
↓Cognitive dysfunctions ↓Aβ deposition ↓Neuroinflammation. |
200 |
| huMSCs | Not given | Neurons | PD | PD rats |
↑Proliferation of SH‐SY5Y cells ↑Autophagy ↑Dopamine level in the striatum ↓Apomorphine‐induced asymmetric rotation ↓Neuron loss and apoptosis |
201 |
| huMSCs | miR‐146a‐5p | Astrocytes | SCI | SCI in rats |
↑Neural tissue preservation ↑Locomotor function of the hindlimbs ↓Inflammatory responses ↓Neurotoxic astrocytes numbers ↓Traf6/Irak1/NF‐κB signaling pathway |
202 |
| huMSCs | miR‐199a‐3p/145‐5p | Neurons | SCI | SCI in rats |
↑NGF/TrkA signaling pathway ↑Locomotor function of SCI rats |
210 |
| huMSCs | Not given |
Neurons/ Microglia |
SCI | SCI in rats |
↑Motor function of SCI rats ↑Wnt/β‐Catenin signaling pathway ↓Apoptosis ↓Inflammatory state from SCI injury |
211 |
| huMSCs | Not given |
Astrocytes/ Microglia |
TBI | TBI in rats |
↑Neurological function recovery ↓Neuronal apoptosis ↓Microglia and astrocytes activation |
203 |
| huMSCs | Not given | Neurons | Stroke | MCAO in rats |
↓Infarct size ↓Ischemic brain damage |
204 |
| DP‐MSCs | Not given | Neurons/ Astrocytes | Stroke | MCAO in rats |
↑Functional recovery ↓Infarct volume ↓Reactive gliosis ↓MAPK and TGF‐β signaling pathway |
212 , 219 |
| SHED | Not given | Microglia | TBI | TBI rats via the “free‐falling method” |
↑Motor functional recovery ↑M2 phenotypic microglia ↓Neuroinflammation ↓M1 phenotypic microglia |
220 , 221 |
| iNPCs | miR‐21a | Neurons | Not given | In vitro | ↑Neurogenesis | 216 |
| iNPCs | Not given | Not given | Not given | Not given |
↑ERK signaling pathway ↑Growth factor‐associated proteins levels |
217 |
Abbreviations. AD, Alzheimer's disease; ADMSCs, adipose‐derived mesenchymal stem cells; ADSCs, adipose‐derived stem cells; AIS, acute ischemic stroke; ALS, amyotrophic lateral sclerosis; BMECs, brain microvascular endothelial cells; BMSCs, bone marrow‐derived mesenchymal stem cells; CCI, controlled cortical impact; DP‐MSCs, dental pulp mesenchymal stem/stromal cells; EBI, early brain injury; hADSCs, human adipose tissue‐derived MSCs; HIBD, hypoxic‐ischemic brain damage; huMSCs, human umbilical cord mesenchymal stem cells; iNPCs, induced neural stem/progenitor cells.; IS, ischemic stroke; MCAO, middle cerebral artery occlusion; PD, Parkinson's disease; SAH, subarachnoid hemorrhage; SCI, spinal cord injury; SHED, stem cells from human exfoliated deciduous teeth; TBI, traumatic brain injury.