Therapeutic potential of mesenchymal stem cells in neurodegenerative diseases

Table 3 Summary of therapeutic efficacy and safety of mesenchymal stem cells and their derivatives in Parkinson’s disease

Animal model	Source	Type	Administration method	Main outcomes	Ref.
C57BL/6 mice with MPTP	Human	hUC-MSCs	IN	Inhibit activated glial cells, repair dopamine neuron degeneration, improve motor behavior in mice	[158]
C57BL/6 mice with 6-OHDA	Human	hUC-MSCs	IN	Upregulate SATB1, activate Wnt/β-catenin pathway, improve motor behavior, reduce neuronal damage	[159]
C57BL/6 mice with 6-OHDA	Human	hUC-MSCs	ST	Increase dopamine levels and improve motor dysfunction	[160]
C57BL/6 mice with 6-OHDA	Human	hUC-MSCs	ST	Improve rotational behavior, provide neuroprotection, exhibit anti-neuroinflammatory effects	[161]
C57BL/6 mice with 6-OHDA	Human	hUC-MSCs-BDNF	IV	Increase neuronal survival rate	[162]
C57BL/6 mice with 6-OHDA	Human	DPSCs	SI	Promote recovery of dopaminergic neurons, reduce dopaminergic neuron loss, improve motor behavior	[163]
C57BL/6 mice with 6-OHDA	Human	DPSCs	IV	Improve rotational and forelimb asymmetry behaviors, enhance anti-apoptotic Bcl-2/Bax axis	[164]
Zebrafish with 6-OHDA	Human	DPSCs	Yolk sac injection	Improve motor dysfunction	[166]
Zebrafish with rotenone	Mice	BM-MSCs	IV	Improve motor and behavioral performance	[167]
C57BL/6 mice with MPTP	Mice	BM-MSCs	IN	Restore dopaminergic neurons in the substantia nigra and nerve terminals in the striatum, improve motor deficits	[168]
C57BL/6 mice with 6-OHDA	Human	OE-MSCs	IN	Improve motor dysfunction	[169]
C57BL/6 mice with MnCl2	Human	hnmMSC-sEVs	IN	Restore motor dysfunction and enhance neurogenesis	[170]
C57BL/6 mice with MPTP	Human	hUC-MSC-Exos	IN	Increase number of dopaminergic neurons in the SNPC region, rescue death of substantia nigra dopaminergic neurons, alleviate inflammatory responses, and improve local microenvironment	[149]
C57BL/6 mice with 6-OHDA	Human	hUC-MSC-Exos	IV and LV	Repair damage to the nigrostriatal dopamine system, inhibit microglial activation	[150]
C57BL/6 mice with MPTP	Human	hUC-MSCs	IV	Alleviate dopaminergic neuron degeneration, exhibit anti-inflammatory effects	[151]
PD patients	Human	OM-MSCs	IT	Promote recovery of neural function, modulate neuroinflammation	[152]
C57BL/6 mice and cells with MPTP	Human	T-MSC-Exos	IV	Protect DA neurons through the Nox4-ROS-Nrf2 axis, maintain function of the nigrostriatal system, improve motor deficits, and reduce oxidative stress	[153]
C57BL/6 mice with MPTP	Human	BM-MSCs	IV	Reduce neuronal loss, damage, and inflammatory responses, inhibit cell apoptosis	[154]
C57BL/6 mice with MPTP	Human	ADSCs	SI	Secrete neuroprotective factors to prevent neuronal damage, reduce dopaminergic neuron loss and alleviate neuroinflammation; protect dopaminergic neurons	[155]
SH-SY5Y cells with rotenone	Human	NI-hADSC-CM	Coculture	Provide neuroprotection, alleviate αSN aggregation	[143]
Moderate PD patients	Human	BM-MSCs	IV	Safe, well tolerated, and not immunogenic	[142]
C57BL/6 mice with AAV 1/2A 53 T-a-syn	Human	BM-MSCs	SI	Reduce αSN levels; protect dopaminergic neurons, modulate microglial cells	[145]
C57BL/6 mice with rotenone	Mice	BM-MSCs	SI, IV	Improve motor function, protection of the nigrostriatal system, and improve striatal dopamine release	[146]

MPTP: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; hUC-MSCs: Human umbilical cord-derived mesenchymal stem cells; IN: Intranasal administration; 6-OHDA: 6-hydroxydopamine; SATB1: Special AT-rich sequence-binding protein-1; ST: Striatal transplantation; BDNF: Brain-derived neurotrophic factor; IV: Intravenous injection; DPSCs: Dental pulp-dirived mesenchymal stem cells; SI: Stereotaxic injection; Bcl-2: B-cell lymphoma 2; Bax: B-cell lymphoma 2-associated X protein; BM-MSCs: Bone marrow-derived mesenchymal stem cells; OE-MSCs: Olfactory ecto-mesenchymal stem cells; hnmMSC-sEVs: Human nasal mucosal mesenchymal stem cells derived small extracellular vesicles; SNPC: Substantia nigra pars compacta; hUC-MSCs-Exos: Human umbilical cord-derived mesenchymal stem cells derived exosomes; LV: Lateral ventricle injection; PD: Parkinson’s disease; OM-MSCs: Olfactory mucosa mesenchymal stem cells; T-MSC-Exos: Trophoblast stage-derived mesenchymal stem cell-derived exosomes; DA: DArgic; Nox4: NADPH oxidase 4; ROS: Reactive oxygen species; Nrf2: Nuclear factor erythroid 2-related factor 2; SH-SY5Y: Human neuroblastoma cell line SH-SY5Y; NI-hADSC-CM: Neural-induced human adipose tissue-derived stem cell-conditioned medium; αSN: α-synuclein.