Skip to main content

Advertisement

Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Table 1 AD rodent model stem cell transplantation studies in the last 5 years

From: Alzheimer’s disease, dementia, and stem cell therapy

Study [23] [24] [26] [27] [34] [35] [36] [37] [38] [39] [45]
Cell type Murine embryonic NSCs Human fetal NSCs Human fetal NSCs Human fetal NSCs Human UCB-MSCs Human PD-MSCs Human U-MSCs
Human U-MSC-NCs
Human A-MSCs Murine BM-MSCs Human BM-MSCs Human iPSC-derived neuronal precursors
Model B6C3-Tg
(APPswe/PSEN1dE9) transgenic mice
NSE-APPswe transgenic mice Tg2576
(APPswe) transgenic mice
3×Tg-AD
transgenic mice
CaM/Tet-DTA mice
APP/PS1 transgenic mice 1–42
cerebrally infused mice
B6C3-Tg
(APPswe/
PSEN1dE9) transgenic mice
Tg2576
(APPswe) transgenic mice
3xTg-AD
transgenic mice
APP/PS1 transgenic mice 1–42
cerebro-ventricular infused mice
PDAPP transgenic mice
Delivery route Bilateral intra-hippocampal stereotactic injection
5 × 105 to 1 × 106 cells Sham: PBS vehicle
Bilateral intra-ventricular stereotactic injection
5 × 105 cells Sham: H-H buffer vehicle
Bilateral intra-hippocampal stereotactic injection
2.5 × 105 cells Sham: culture media vehicle
Bilateral intra-hippocampal stereotactic injection
1 × 105 cells Sham: vehicle
Three bilateral intra-hippocampal injections at 2 week intervals
1 × 105 cells per injection Sham: PBS vehicle
Intravenous injection
1 × 105, 5 × 105, or 1 × 106 cells Sham: Saline vehicle
Bilateral intra-hippocampal stereotactic injection
5 × 104 cells Sham: PBS vehicle
Intravenous injection
2 × 106 cells Sham: PBS vehicle
Intravenous injection
1 × 106 cells Sham: NaCl solution vehicle
Intravenous injection
1 × 106 cells Sham: PBS vehicle
Bilateral intra-hippocampal stereotactic injection
2 × 105 cells Sham: PBS vehicle
Findings 10 weeks post-operation
Extensive donor cell migration
14.6% neuron, 36.2% astrocyte, and 28.5% oligodendroctye phenotypic differentiation
Improved spatial memory (Morris water maze)
Decreased expression of pro-inflammatory cytokines IL-1β, IL-6, TNF-α and PGE2
Aβ levels unchanged
7 weeks post- operation
Extensive donor cellular migration
NSC phenotype remained in >80% of cells
Improved spatial memory (Morris water maze)
Decreased levels of phosphorylated tau, Aβ plaques, astrogliosis, microgliosis and apoptosis
Decreased expression of pro-inflammatory cytokines IL-1β, IL-6, TNF- α and iNOS
Increased cerebral neurotrophin levels and increased hippocampal synaptic density
5 weeks post- operation
Donor cells in the dentate gyrus polymorphic layer
70% neuron, 20% astrocyte phenotypic differentiation
Improved spatial memory (Morris water maze)
Increased endogenous neurogenesis in the dentate gyrus
Reduced cerebral Aβ levels
6 weeks post-operation
Donor cells in the CA1 hippocampal subregion
36.6% and 41.1% cell survival in 3 × Tg-AD and CaM/Tet-DTA, respectively
Improved spatial memory (Morris water maze, context- and place-dependent NOR task)
Majority of donor cells expressed NSC phenotype
Increased levels of synaptic proteins in the hippocampus
Soluble, insoluble and hyperphosphorylated tau, Aβ40, and Aβ42 levels unchanged
41 days post-operation (first injection)
Improved spatial memory (Morris water maze)
Reduced phosphorylated tau, Aβ plaques, vascular Aβ40, and BACE-1 expression in the cortex and hippocampus
Increased levels of activated microglia in the cortex and hippocampus
Reduced levels of pro-inflammatory cytokines IL-1β and TNF-α, and increased anti-inflammatory cytokine IL-4
2 weeks post-operation
Limited donor cells in the hippocampus, and no neural differentiation
Improved spatial memory (Morris water maze)
Reduced levels of cerebral APP and BACE1, and reduced β- and γ-secretase activity
Reduced levels of activated astrocytes and microglia
Attenuation Aβ1–42 induced hippocampal apoptosis, and impaired endogenous neuronal differentiation
Reduced expression of inflammatory proteins iNOS and COX-2, and an array of pro-inflammatory cytokines
4 weeks post-operation
No donor cells present at 4 weeks post-surgery
Improved spatial memory (Morris water maze) in the U-MSC-NC group
Increased hippocampal levels of synapsin I in the U-MSC-NC group
Decreased hippocampal Aβ deposition, decreased soluble Aβ40 and Aβ42 levels, and increased Aβ-degrading enzymes in the U-MSC-NC group
Increased number of M2 activated microglia in the U-MSC-NC group
Reduced pro-inflammatory cytokines (IL-1β and TNF-α), and increased anti-inflammatory cytokine IL-4 in the U-MSC-NC group
6 weeks post-operation (Tg2576 mice)
Improved spatial memory (Morris water maze)
1 and 12 weeks post-operation (3 × Tg-AD mice)
Donor cells in the spleen, lung, liver, but not brain
Reduced number and size of Aβ plaques
Increased density of activated microglia in the hippocampus by week 1, lower density than in sham animals by week 12
Increased phagocytotic microglia
Reduced proinflammatory cytokines IL-1 and TNF-α at week 1
Increased anti-inflammatory cytokines IL-10 and TNF-β at week 12
Increased levels of Aβ-degrading enzymes
1 and 4 -weeks post-operation
Donor cells in the cerebral cortex and hippocampus, bone marrow, lung, and liver
No reduction in total Aβ levels
Reduced total levels and vascular deposition of pE3-Ab protein at 4 weeks
Increased number of <50 μm Aβ plaques, and reduced number of 50–100 μm Aβ plaques
Reduced levels of activated astrocytes and ramified microglia
Reduced levels of cortical and hippocampal microglia
Reduced levels of hippocampal TNF-α, IL-6, and elevated levels of hippocampal PTGER2
1, 2, and 4 weeks post-operation
Donor cell neuronal differentiation in the entorhinal cortex and hippocampus
Improved working memory performance (Radial Arm Maze)
Attenuation of impaired neurogenesis and neuronal differentiation in the hippocampus at 2- and 4-week time points
Increased hippocampal expression of neural specification proteins β-catenin and Ngn1
2 weeks post-operation
Improved spatial memory (Morris water maze)
45 days post-operation
Improved spatial memory (Morris water maze)
Donor cell survival and neuronal differentiation in the hippocampus
Donor cells expression of cholinergic and GABAergic neuronal markers
Therapeutic mechanism Modulation of inflammation Modulation of inflammation and microglia immune response, and protection from Aβ neurotoxicity Neurotrophic support of endogenous neurogenesis and synaptic connectivity Neurotrophic support of endogenous neurogenesis and synaptic connectivity Modulation of inflammation and microglia, and anti-amyloidogenic Neurotrophic support of endogenous neurogenesis, modulation of inflammation and microglia immune response, and anti-amyloidogenic Modulation of inflammation and microglia immune response Modulation of inflammation and microglia immune response Modulation of microglia immune response Neurotrophic support of endogenous neurogenesis
and protection from Aβ neurotoxicity
Regeneration of depleted neural networks
  1. amyloid beta, AD Alzheimer’s disease, A-MSC adipose-derived mesenchymal stem cell, BM-MSC bone marrow-derived mesenchymal stem cell, COX cyclooxygenase, GABA gamma-aminobutyric acid, H-H Henderson-Hasselbalch, IL interleukin, iNOS inducible nitric oxide synthase, iPSC induced pluripotent stem cell, Ngn neurogenin, NOR novel object recognition, NSC neural stem cell, PBS phosphate-buffered saline, PD-MSC placenta-derived mesenchymal stem cell, PGE prostaglandin, PTGER prostaglandin E receptor, TNF tumour necrosis factor, U-MSC umbilical cord Warton’s jelly-derived mesenchymal stem cell, U-MSC-NC neuron-like cell differentiated from umbilical cord Warton’s jelly-derived mesenchymal stem cell, UCB-MSC umbilical cord blood-derived mesenchymal stem cell