Therapeutic potential of mesenchymal stem cells in neurodegenerative diseases

Table 2 Summary of therapeutic efficacy and safety of mesenchymal stem cells and their derivatives in Alzheimer’s disease

Animal model	Source	Type	Administration method	Main outcomes	Ref.
C57BL/6 mice with Aβ25-35	Mice	BM-MSCs	IV	Upregulate BDNF expression, downregulate GSK-3β activity, improve cognitive dysfunction	[116]
C57BL/6 mice with Aβ25-35	Mice	BM-MSCs	IV	Inhibit microglial activation, improve behavioral deficits, reduce neuroinflammatory cytokines	[115]
APP/PS1 mice	Human	hUC-MSCs, SHED, ADSCs	IV	Reduce amyloid plaques, improve behavioral deficits, and increase neuronal and Nissl body density in brain regions	[117]
APPswe/PS1dE9 mice	Human	OM-MSCs	SI	Alleviate AD symptoms and promote Aβ clearance	[118]
C57BL/6 mice with Aβ1-42	Human	BM-MSC-EVs	SI	Stimulate neurogenesis in the subventricular zone, alleviate cognitive impairment	[121]
C57BL/6 mice with STZ	Human	iPSC-MSC-sEVs	SI	Alleviate neuroinflammation, reduce amyloid deposition and neuronal apoptosis, and mitigate cognitive dysfunction	[120]
C57BL/6 mice with AlCl3	Mice	BM-MSC-EVs	IP	Regulate autophagy through the PI3K/AKT/mTOR pathway, promote Aβ degradation, modulate immunity, and improve memory and neurological dysfunction	[122]
C57BL/6 mice with AlCl3	Mice	ADSC	IV	Reduce amyloid deposition, mitigate cognitive dysfunction	[119]
Zebrafish with LPS	Human	ADSC-EVs	IV	Reduce LPS-induced inflammatory cytokines	[123]
C57BL/6 mice with Aβ1-42	Mice	BM-MSCs	IV	Induce mitophagy in neuronal cells, alleviating mitochondrial damage-mediated apoptosis and NLRP3 inflammasome activation	[125]
C57BL/6 mice with STZ	Mice	BM-MSC-Exos	SI	Modulate hippocampal glial cell activation, alleviate neuroinflammation, mitigate cognitive dysfunction	[127]
APP/PS1 mice	Human	hUC-MSCs	IV	Inhibit glial cell activation and oxidative stress	[128]
APP/PS1 mice	Mice	BM-MSCs	HIPP injection	Reduce number of Aβ plaques and increase M2 microglial polarization	[101]
C57BL/6 mice	Mice	BM-MSCs	SI	Stimulate endogenous neurogenesis	[130]
C57BL/6 mice with Aβ1-42	Human	OE-MSCs	IN	Upregulate BDNF and NMDAR; reduce neuronal loss	[132]
C57BL/6 mice with STZ	Human	hUC-MSC-Exos	IV	Increase adiponectin levels and protect neurons	[133]
C57BL/6 mice with AlCl3	Mice	ADSCs	IV	Reduce amyloid deposition, mitigate cognitive dysfunction	[119]
SH-SY5Y cell with Aβ1-40	Human	Exosomes derived from the serum of AD patients	Coculture	Reduce apoptosis through the PI3K/AKT signaling pathway	[134]
APP/PS1 mice	Human	hUC-MSCs	IV	Enhance targeting ability of hUC-MSCs and promote production of neuroprotective factors; improve cognitive function	[136]

Aβ: Amyloid-β; BM-MSCs: Bone marrow-derived mesenchymal stem cells; IV: Intravenous injection; BDNF: Brain-derived neurotrophic factor; GSK-3β: Glycogen synthase kinase-3 beta; APP: Amyloid precursor protein; hUC-MSCs: Human umbilical cord-derived mesenchymal stem cells; SHED: Stem cells from human exfoliated deciduous teeth; ADSCs: Adipose-derived mesenchymal stem cells; OM-MSCs: Olfactory mucosa mesenchymal stem cells; SI: Stereotaxic injection; AD: Alzheimer’s disease; BM-MSC-EVs: Bone marrow mesenchymal stem cell-derived extracellular vesicles; STZ: Streptozotocin; iPSC-MSC-sEVs: Induced pluripotent stem cells-derived mesenchymal stem cell-derived small extracellular vesicles; AlCl₃: Aluminum chloride; IP: Intraperitoneal injection; PI3K: Phosphatidylinositol 3-kinase; AKT: Proteinkinase B; mTOR: Mechanistic target of rapamycin; LPS: Lipopolysaccharide; ADSC-EVs: Adipose-derived mesenchymal stem cell-derived extracellular vesicles; BM-MSC-Exos: Bone marrow-derived mesenchymal stem cells-derived exosomes; NLRP3: NOD-like receptor family, pyrin domain containing 3; HIPP: Hippocampus; IN: Intranasal administration; OE-MSCs: Olfactory ecto-mesenchymal stem cells; NMDAR: N-methyl-D-aspartate receptor; hUC-MSC-Exos: Human umbilical cord-derived mesenchymal stem cell-derived exosomes.