Neural stem cell therapy for brain disease

Table 1 Therapeutic potential of stem cell transplantation in Alzheimer’s disease models

	Animal model	Transplanted cells	Density of transplanted cells	Transplantation site	Therapeutic effects	Unique features	Results	Ref.
1	Mice (Transgenic 3 x Tg- AD and Thy1-APP)	NSCs	100000 cells in 2 µL	Hippocampus	Aβ-clearance, increased synaptic density	Neprilysin gene transfer	Not assessed	Blurton-Jones et al[37]
2	Mouse (NBM lesion)	ESC-derived neurosphere	400 µL/injection, 1-5 × 104 cells/µL	Prefrontal and parietal cortices	ChAT and serotonin-positive neurons	ChAT + cells↑	Working memory ↑	Wang et al[27]
3	Rat (Forebrain), Okadaic acid	NSC (rat)	5 µL /injection site (2 injections) 2 × 104 cells/mL	Hippocampus and cerebral cortex	replace damaged or lost neuron	NGF(human), gene transfer	Memory ↑	Wu et al[28]
4	Mice (Transgenic Tg2576)	MSCs from human UCB	100000 cells/ Mouse (i.v.)	Systematic	Anti-inflammatory, anti-amyloidogenic	None	Not assessed	Nikolic et al[29]
5	Rat (NBM lesion) Ibotenic acid	ESC-derived NPC (mouse)	2 × 105 cells in 2 µL	Forebrain specially NBM	Forming cholinergic cell phenotype	Shh-primed	Water maze↑; Spatial probe↑	Moghadam et al[30]
6	Mouse (3X TG-AD)	NSC (mouse)	100000 murine NSCs	Hippocampus	Neurotropic effects	BDNF-mediated effect	Working memory↑	Blurton-Jones et al[31]
7	Rat (Hippocampus) Kainic acid	Immortalized NSC (human, HB1.F3)	1 × 106 cells/rat	Hippocampal CA3 region	Migrate to injured site differentiate into neurons overexpressing ChAT	ChAT (human), gene transfer	Water maze↑; Spatial probe↑	Park et al., 2012a[33]
8	Rat (NBM lesion) AF64A toxin	Immortalized NSC (human, HB1.F3)	1 × 106 cells/rat	ICV	migrate to various brain regions including cerebral cortex and hippocampus	ChAT (human) gene transfer	Water maze↑; Spatial probe↑	Park et al[32]
9	Mice (Transgenic APP/PS1)	MSCs from human UCB	1 × 105 cells in 3 µL(3 injection once after 2 wk)	Hippocampus	Anti-inflammatory, anti-amyloidogenic, anti-phosphorylation of tau	None	Improved learning and memory	Lee et al[34]
10	Mouse (Hippocampus) Ibotenic acid	Immortalized NSC (human, HB1.F3)	2 × 105 cell suspension 2 µL	Hippocampus	migrated to lesion sites and differentiated into neurons and astrocytes	NGF (human); Gene transfer	Water maze↑; Spatial probe↑	Lee et al[35]
11	Mice (Transgenic APP/PS1)	MSCs from human UCB	2 × 104 cells per head	Hippocampus, cortical region	Anti-inflammatory, Aβ-clearance	-	Not assessed	Kim et al[36]

NBM: Nucleus basalis of Meynert; ESC: Embryonic stem cell; NGF: Nerve growth factor; 3XTG: Triple transgenic/APP-presenilin-tau; BDNF: Brain-derived growth factor; ChAT: Choline acetyltransferase; NPC: Neural precursor cell; NSC: Neural stem cell; SHH: Sonic hedgehog protein; UCB: Umbilical cord blood; Aβ: Beta-amyloid; MSCs: Mesenchymal stem cells; APP: Amyloid-β precursor protein; ICV: Intra-cerebro ventricular.

Table 2 Therapeutic potentials of stem cell transplantation in Parkinson's disease models

	Disease model	Source of transplanted cells	Transplantation location	Density of transplanted cells	Unique feature or treatment	Results	Ref.
1	Rat, 6-OHDA	Immortalized NSC (mouse, C17-2)	Striatum	106 cells	TH/GTPCH1; Gene transfer	Rotation↓	Ryu et al[48]
2	Monkey, MPTP	ESC (monkey)	Bilateral putamen	3 x 105-6 x 105 cells per side	Stromal cell (mouse) feeder	PFS-parkinsonian factor score↓	Takagi et al[49]
3	Rat, 6-OHDA	Immortalized NSC (human, HB1.F3)	Striatum	3 × 105 cells/3 μL	TH/GTPCH1 gene transfer	Rotation↓	Kim et al[50]
4	Rat, 6-OHDA	Immortalized NSC (human, HB1.F3)	Striatum	2 x 105/3µL	NSC migration	Rotation↓	Yasuhara et al[51]
5	Rat, 6-OHDA	MSCs from human UCB	Striatum	1 × 105 cells/10 µL	FGF8/SHH	Rotation↓	Fu et al[52]
6	Rat, 6-OHDA	DA neurons from ESC (human)	Striatum	5 x 105 cells	None	Rotation↓, beam walking↓	Cho et al[53]
7	Mice, 6-OHDA	DA neurons from ESC (human)	Striatum	1.5 × 105 cells /1.5 µL	Wnt signal; SHH	Rotation↓	Kriks et al[54]
8	Mice, 6-OHDA	iNSCs (rat)	Striatum	1 × 105 cells	Tripotential differentiation capacity	Rotation↓	Choi et al[42]

6-OHDA: 6-hydroxydopamine; MSC: Mesenchymal stem cell; ESC: Embryonic stem cell; FGF8: Fibroblast growth factor 8; GTPCH-1: GTP cyclohydrolyrase-1; MPTP: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; iNSC: Induced neural stem cell; TH: Tyrosine hydrpxylase; NTN: Neurturin; UC: Umbilical cord blood; SHH: Sonic hedgehog protein; CN: Caudate nucleus; SN: Substantia nigra.