Table 1.

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

Disease/Disorder	Reference	Animal Model	Cell Source	Dose	Route of Administration	Biological/Medical Improvement	Suggested Mechanism of Action
Alzheimer’s	[52]	Ovariectomized albino-rat	Rat BM	100 μg	Intravenous (IV)	Improved in destructive structural changes in the taste buds and their innervations	Improved synaptophysin-immunoreactivity
Alzheimer’s	[45]	APP/PS1 mouse	Mouse BM	22.4 µg	Intracerebral	Reduced amount of dystrophic neurites in both the cortex and hippocampus	Aβ plaque reduction
Alzheimer’s	[49]	Streptozotocin-induced mouse	Mouse BM	0.5 μg/day for 5 days	Intraventricular	Recovered cognition impairment	Not mentioned
Alzheimer’s	[46]	APP/PS1 mouse	Mouse BM	100 μg	Intracerebroventricular	Improved cognitive behavior, rescued impairment of CA1 synaptic transmission, and long-term potentiation	Suppression of Aβ induced iNOS expression
MS	[28]	EAE rat	Rat BM	100/400 μg	IV	Decreased neural behavioral scores	Reduced demyelination and neuroinflammation
Stroke	[32]	Subcortical infarction rat	Rat adipose	50/100/200 μg	IV	Improved functional outcomes associated with decreased cell death	Restored fiber tract connectivity, increased oligodendrocyte markers, and re-myelination
Stroke	[33]	MCAo rat	Rat BM	120.68 μg	IV	Reduced neurological severity score; improved spatial learning and memory ability	Inhibited the expression of CysLT2R and NMLTC4 treated microglia; modulated the balance between M1 and M2 microglia; decreased pro-inflammatory cytokines secretion; increased anti-inflammatory and neurotrophic factors production
Stroke	[53]	Cortical injured monkey	Monkey BM	4 × 1011 particles/kg	IV	Enhanced recovery of fine motor function	Not mentioned
Stroke	[40]	MCAo rat	Adipose (cell source not mentioned)	3 treatments of 2.0 × 106 particles	IV	Reduced infarct volume; suppressed apoptosis	Improved BBB condition; suppressed inflammation; reduced abnormal high level of miR-21-3p
Stroke	[54]	Intracerebral hemorrhage injection rat	Rat BM	100 µg	IV	Improved spatial learning, motor function, and sensory memory	Promoting endogenous angiogenesis and neurogenesis; increased white matter remodeling
Stroke	[70]	tMCAo rat	Rat BM	30 µg	IV	Improved Neurological function	Promoted neurogenesis and angiogenesis via miR-184 and miR-210, respectively
Stroke	[34]	Intracerebral hemorrhage rat	Rat adipose	100 µg	IV	Improved functional recovery; reduced infarct size	Increased fiber tract and axonal sprouting; enhanced oligodendrocyte formation and remyelination
Stroke	[47]	Transient global cerebral ischemia mouse	Mouse BM	200 µg	Intracerebroventricular	Restored impaired basal synaptic transmission and synaptic plasticity, and improved spatial learning and memory	Inhibited pathogenic expression of COX-2 in the hippocampus
Stroke	[35]	Subcortical infarct rat	Rat adipose	100 µg	IV	Improved functional recovery	Increased axonal sprouting and growth, oligodendrocyte formation, tract connectivity and remyelination
Stroke	[36]	MCAo rat	Mini-pig adipose	100 µg	IV	Reduced brain infarct zone; improved neurological function	Suppressed inflammation; reduced ROS and oxidative stress generation; promoted angiogenesis
Stroke	[69]	MCAo rat	Rat BM	100 µg	IV	Improved neurologic outcome	Enhanced neurite remodeling, neurogenesis, and angiogenesis
Neuroinflammation	[44]	LPS-induced rat	Rat BM	200 µg	IV	Enhanced neuronal survival	Reduced oxidative stress; reduced inflammatory response
TBI	[41]	Controlled cortical impact (CCI) mouse	Rat BM	30 µg	Retro-orbital	Improved functional recovery; reduced cortical lesion volume; attenuated cellular apoptosis	Inhibited early neuroinflammation through modulation of microglia/macrophages polarization
TBI	[59]	CCI rat	Rat BM	100 µg	IV	Cognitive and sensorimotor improvement.	Promotion of endogenous angiogenesis and neurogenesis; and inflammation reduction.
SCI	[38]	Spinal cord hemisection rat	Rat BM	100 µg	IV	Improved functional recovery and attenuated lesion size and apoptosis	Targeted inhibition of the FasL gene by miR-21-5p
SCI	[42]	Rat contusive SCI	Rat BM	1 × 106 cells equivalents	IV	Reduced neuronal cell apoptosis, enhanced neuronal survival and regeneration, and improved motor function	Suppression of pericytes migration; and improved blood-spinal cord barrier integrity via NF-κB p65 signaling
SCI	[39]	Rat contusive SCI	Rat BM	100 µg	IV	Suppressed glial scar formation; attenuated lesion size; promoted axonal regeneration; and improved functional behavioral recovery	Promoted blood vessel formation; reduced neuronal cells apoptosis; suppressed inflammation; and suppressed activation of A1 neurotoxic reactive astrocytes
SCI	[30]	Spinal cord hemisection injured rat	Rat BM	100 µg	IV	Reduced disease severity	Inhibited complement mRNA synthesis and release; inhibited activation of NF-κB signaling by binding to microglia cells.
SCI	[48]	Rat contusive SCI	Rat BM	1 × 106 cells equivalents	IV	Improved locomotor function; and the neuroprotective effect on residual neurons, synapses, and myelin sheath.	Reduced A1 astrocyte proportion by inhibiting NFκB activation; reductions in proinflammatory cytokine levels
SCI	[31]	Rat contusive SCI	Rat BM	100 µg	IV	Attenuated lesion size and improved functional recovery	Attenuated cellular apoptosis and inflammation; promoted angiogenesis