Therapeutic potential of mesenchymal stem cells in neurodegenerative diseases

Table 5 Summary of therapeutic efficacy and safety of mesenchymal stem cells and their derivatives in amyotrophic lateral sclerosis

Animal model	Source	Type	Administration method	Main outcomes	Ref.
In vitro SIM-A9 hSOD1 (G93A) microglial cells	Mice	ADSCs	Coculture	Reduce metabolic activity of microglia, decrease iNOS+ cells, and increase CD206+ cells	[176]
BV-2 cells with SOD 1-G93 A	Human	hUC-MSC-CM	IV	Extend lifespan and reduce expression of pro-inflammatory cytokines and iNOS	[178]
SOD 1G 93 A mice	Human	BM-MSCs	IV	Mediate anti-inflammatory responses through the CX3CL1/CX3CR1 axis	[179]
SOD 1G 93 A mice	Mice	BM-MSCs	IV	Upregulate expression of Nrf2 and NQO1, promote antioxidant responses, and reduce accumulation of reactive oxygen species	[180]
ALS patients	Human	BM-MSCs	IT	Feasible and safe	[181]
ALS patients	Human	BM-MSCs	IT, IV	Feasible and safe	[182]
ALS patients	Human	BM-MSCs	IT	Feasible and safe	[183]
hSOD 1 G93 A mice	Human	hUC-MSCs	IM	Extend lifespan; enhance motor function	[184]
ALS cell model expressing TDP-43 mutant M337V	Human	hUC-MSCs	Coculture	Activate the Nrf-2/HO-1 axis to exert antioxidant and neuroprotective effects	[185]
SOD 1G 93 A-NSC 34 cell model	Human	hUC-MSCs	Coculture	Inhibit the NF-κB/Bcl-2 signaling pathway; reduce cell apoptosis	[186]
ALS patients	Human	hUC-MSCs	IT	Feasible and safe	[187]
ALS patients	Human	ADSCs	LP	Feasible and safe	[188]
ALS patients	Human	hUC-MSCs	IN	Feasible and safe, lifespan extended by 2-fold	[189]
SOD 1G 93 A rat	Human	BM-MSCs	IT, IM	Increase survival of motor neurons	[190]
SOD 1G 93 A mice	Mice	BM-MSCs	IV	Reduce astrocyte activation and expression of neuroinflammatory factors	[180]
SOD 1G 93 A rat	Not mentioned	BM-MSCs	IV	Prolong survival period and protect the motor function	[191]
SOD 1G 93 A mice	Human	ADSCs	IV	Delay disease progression, prolong survival rate, and enhance neuron survival	[192]
SOD 1G 93 A mice	Human	iPSC-sEVs	IN	Improve motor performance and survival time	[193]

SOD1: Superoxide dismutase 1; ADSCs: Adipose-derived mesenchymal stem cells; iNOS: Inducible nitric oxide synthase; CD206: Cluster of differentiation 206; SOD 1-G93 A: Superoxide dismutase 1 with glycine 93 to alanine mutation; hUC-MSC-CM: Human umbilical cord-derived mesenchymal stem cell-conditioned medium; IV: Intravenous injection; BM-MSCs: Bone marrow-derived mesenchymal stem cells; CX3CL1: C-X3-C motif chemokine ligand 1; CX3CR1: C-X3-C motif chemokine receptor 1; Nrf2: Nuclear factor erythroid 2-related factor; NQO1: NAD(P)H quinone dehydrogenase 1; ALS: Amyotrophic lateral sclerosis; IT: Intrathecal injection; hUC-MSCs: Human umbilical cord-derived mesenchymal stem cells; IM: Intramuscular injection; TDP-43: Transactive response DNA-binding protein 43; HO-1: Heme oxygenase-1; NF-κB: Nuclear factor-kappa B; Bcl-2: B-cell lymphoma 2; LP: Lumbar puncture; iPSC-sEVs: Induced pluripotent stem cell-derived small extracellular vesicles.