Table 2.

Naïve human MSC-derived exosomes in animal models of neurodegeneration.

Disease/Disorder	Reference	Animal Model	Cell Source	Dose	Root of Administration	Biological/Medical Improvement	Suggested Mechanism of Action
Alzheimer’s	[50]	Aβ-inoculated mouse	Human, purchased from ATCC	10 µg	Intrahippocampal	Enhance neurogenesis and restore cognitive function	Not mentioned
Alzheimer’s	[51]	APP/PS1 mouse	Human umbilical cord	30 µg	IV	Repair cognitive disfunctions	Help to clear Aβ deposition; and modulate the activation of microglia in the brain
MS	[29]	EAE mouse	Human BM	150 μg	IV	Reduced disease severity	Reduced demyelination; decreased neuroinflammation; and upregulated the number of regulatory T cells
Stroke	[55]	MCAo rat	Human umbilical cord blood	150 µg	IV	Attenuated infarct size; exacerbated the somatosensory and motor dysfunction	Not mentioned
Stroke	[37]	MCAo mouse	Human BM	Released by 2 × 106 MSCs	IV	Improved neurological impairment and long-term neuroprotection	Promoted neurogenesis and angiogenesis; prevented post-ischemic immunosuppression
Perinatal brain injury	[56]	A combination of a hypoxic-ischemic and an inflammatory insult in rat	Human Wharton’s jelly	50 mg/kg	Intranasal (IN)	Improved long-term neurodevelopmental outcome	Prevented gray and white matter alterations
Perinatal brain injury	[43]	Rice-Vannucci mouse	Human BM	1.25 × 109 particles/dose	IN	Improved short-term behavioral outcomes; reduced tissue volume loss and cell death	Reduced microglial activation
Perinatal brain injury	[57]	LPS-induced rat	Human BM	1 × 108 cell equivalents/kg bodyweight	Intraperitoneal (IP)	Improved long-lasting cognitive functions	Ameliorated inflammation-induced neuronal cellular degeneration; reduced microgliosis; prevented reactive astrogliosis; and restored short-term myelination deficits and long-term microstructural abnormalities of the white matter
Perinatal brain injury	[58]	Transient umbilical cord occlusion in preterm ovine fetus	Human BM	Two boluses of 2.0 × 107 cell equivalents	IV	Reduced total number and duration of seizures; and preserved baroreceptor reflex sensitivity	Hypomyelination prevention
TBI	[61]	A combination of CCI and hemorrhagic shock swine	Human BM	1 × 1013 particles	IV	Reduced the severity of neurological injury and improved neurocognitive recovery	Not mentioned
TBI	[60]	CCI mouse	Human BM	30 µg	IV	Rescued pattern separation and spatial learning impairments	Immunomodulation
SCI	[62]	Mouse contusive SCI	Human umbilical cord	20/200 µg	IV	Promoted locomotor functional recovery	Attenuated inflammation of the injury region
SCI	[63]	Spinal cord contusion rat	Human BM	1 × 109 particles	IV	Improved locomotor recovery score; improved mechanical sensitivity	Diminished inflammatory response
SE	[64]	Pilocarpine mouse	Human umbilical cord	30 µg	Intraventricular	Ameliorated learning and memory impairments	Reduced inflammatory responses associated with hippocampal astrocyte activation via Nrf2-NF-κB signaling pathway
SE	[65]	Pilocarpine mouse	Human BM	30 µg	IN	Long-term preservation of normal hippocampal neurogenesis and cognitive and memory function	Diminished loss of glutamatergic and GABAergic neurons; and reduced inflammation in the hippocampus