Table 3.

MSC-derived secretome (e.g., exosome) therapy in preclinical models of common neurodegenerative diseases

Condition	Model	Cell source	Administration route	Results	Ref.
AD	3xTg mice	BM	Intranasal	Induction of neuroprotection by provoking anti-inflammatory effect	[92]
AD	APP/PS1 mice	BM	Intravenous	Amelioration in learning and memory capabilities, reducing Aβ levels and supporting anti-inflammatory environment	[217]
AD	APP/PS1 mice	BM	Intravenous	Cognitive impairment rescue by improving microRNA-146a levels in the hippocampus	[105]
AD	Aluminum chloride-injected rat	BM	Intravenous	Pathological symptoms rescue	[218]
PD	6-OHDA rat	BM	Intravenous	Attenuation of dopaminergic neuron loss in SN, and improving dopamine levels in the striatum	[93]
PD	6-OHDA rat	BM	Intravenous	Neuroprotective effect on dopaminergic neuron	[219]
PD	MPTP mice	AT	Intravenous	Suppression of autophagy and pyroptosis	[155]
PD	MPTP mice	AT	Intraperitoneal	Promotion of the angiogenesis of human brain microvascular endothelial cells (HBMECs)	[95]
PD	6-OHDA rat	AT	NA	Induction of neuroprotection by upregulation of the sirtuin 3 (SIRT3) levels	[220]
PD	6-OHDA rat	BM	Intravenous	Improving motor function	[221]
PD	6-OHDA rat	BM	Intranigral Intrastriatal	Reverting motor phenotype and the neuronal organization	[222]
PD	α-Syn induced C. elegans	BM	NA	Reduced number of α-syn inclusions	[153]
HD	R6/2 mice	AM	Intraperitoneal	Amelioration of neurological complications rotarod function	[162]
ALS	SOD1G93A mice	AT	Intravenous Intranasal	Inhibition of glial cells activation, supporting motor neuron rescue, and protecting the neuromuscular junction	[161]

MSCs, mesenchymal stromal cells; AD, Alzheimer’s disease; PD, Parkinson’s disease; ALS, amyotrophic lateral sclerosis; HD, Huntington’s disease; BM, bone marrow; 6-OHDA, 6-hydroxydopamine; MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Aβ, amyloid beta peptide; AM, amniotic membrane