Table 2.

Genetically modified MSC therapy in preclinical models of common neurodegenerative diseases

Condition	Model	Cell source	Gene	Administration route	Results	References
AD	APP/PS1 mice	BM	CX3CL1 Wnt3a	Intraventricular	Amelioration of learning and memory function	[107]
AD	APP/PS1 mice	BM	lin28B	Intraventricular	Stimulation of MSCs proliferation in vivo, reducing cognitive deficits, enhancing the elimination of Aβ, attenuation of microglia activation and neuronal cell death	[106]
AD	APP/PS1 mice	BM	MiR-937	Intrahippocampal	Augmenting brain-4 secretion by MSCs	[211]
PD	6-OHDA mice	BM	Nurr1	Intrastriatal	Improving the frequency of TH-positive cells in SN, suppression of glial cells activation, and downregulation of the expression of pro-inflammatory factors	[119]
PD	6-OHDA mice	AT	GDNF	Intrastriatal	Improving behavioral phenotype	[67]
AD	APP/PS1 mice	BM	VEGF	Intraventricular	Attenuation of cognitive impairment	[68]
PD	6-OHDA mice	AT	GDNF	Intrastriatal	Enhancing TH- and NeuN-positive cell	[118]
AD	APP/PS1 mice	BM	TREM2	Intraventricular	Improvement of learning and memory function by upregulation of TREM2 and DAP12 gene expression	[212]
AD	Amyloid β rat	BM	BDNF	Intraventricular	Improving cognitive function	[69]
AD	APP/PS1 mice	BM	let-7f-5p	Intraventricular	Extending the retention time of MSCs in brain	[213]
PD	MPTP mice	AT	miR-188-3p	Intravenous	Hindrance of autophagy and pyroptosis process by downregulation of CDK5 and NLRP3	[155]
PD	Rotenone rat	UC	VEGF	Intrastriatal	Attenuation of dopaminergic neuron loss	[120]
ALS	S SOD1G93A mice	UC	BDNF	Intrathecal	Improved lifespan by promotion of motor functions	[72]
PD	6-OHDA rat	WJ	PARKIN	Intrastriatal	Downregulation of the expression of c-JUN, PUMA, AIF, and caspase-3, and maintaining the mitochondrial ΔΨm, thereby inducing neuroprotective effect	[214]
PD	6-OHDA rat	BM	Neurturin	Intrastriatal	Enhancing dopamine synthesis and eliciting dopaminergic neuron protection	[215]
PD	6-OHDA rat	BM	Persephin	Intrastriatal	Promoted levels of dopamine in the striatum	[216]
PD	MPTP monkeys	BM	BDNF	Intrastriatal	Promoted levels of dopamine in the striatum	[70]
HD	YAC128 mice	BM	BDNF	Intrastriatal	Decreased striatal atrophy	[71]

MSCs, mesenchymal stromal cells; AD, Alzheimer’s disease; PD, Parkinson’s disease; ALS, amyotrophic lateral sclerosis; HD, Huntington’s disease; BM, bone marrow; UC, umbilical cord; AT, adipose tissue; WJ, Wharton’s jelly; 6-OHDA, 6-hydroxydopamine; MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Aβ, amyloid beta peptide; SVZ, subventricular zone; GDNF, glial cell line-derived neurotrophic factor; BDNF, brain-derived neurotrophic factor; TH, thymidine hydroxylase; VEGF, vascular endothelial growth factor; IGF-1, insulin like growth factor-1; GFAP, G fibrillary acidic protein; miRs, microRNAs; Nurr1, nuclear receptor related 1; DAP12, DNAX-activating protein of 12 kDa; NLRP3, NOD-like receptor containing pyrin domain 3; NeuN, neuronal nuclei; CDK5, cyclin-dependent kinase 5; PUMA, P53 upregulated modulator of apoptosis; AIF, apoptosis-inducing factor; TREM2, triggering receptor expressed on myeloid cells 2; CX3CL1, chemokine (C-X3-C motif) ligand 1