|
| Cell type | Model | Study design | Findings |
|
| Human WJ-MSCs | 5XFAD | Injection of WJ-MSCs or AgRP directly into the left hippocampus of 5XFAD mice. | Improves proteasome activity by AgRP.
Reduces the accumulation of ubiquitin-conjugated proteins [32]. |
|
| Human WJ-MSCs | APP/PS1 | Injection of WJ-MSCs into the tail vein of APP/PS1 mice. | Improves the spatial learning.
Mitigates memory decline.
Increases IL-10.
Reduces Aβ deposition levels.
Reduces soluble Aβ levels.
Proinflammatory microglial activation.
Reduces IL-1β and TNFα levels [33]. |
|
| Human WJ-MSCs | 5XFAD | I.V.T. infusion of WJ-MSCs (exposed to an AD cell line) into 5XFAD mice. | Reduces cell death
Reduces ubiquitin conjugate levels
Reduces Aβ levels [34]. |
|
| Human UCB-MSCs | 5XFAD | Infusion of recombinant human GAL-3 protein and UCB-MSCs into 5XFAD mice. | Improves the spatial learning.
Improves memory impairment.
UCB-MSCs mitigate hyperphosphorylation of tau through GAL-3 secretion [35]. |
|
| Human UCB-MSCs | APP/PS1 | Coculture of UCB-MSCs with NSCs to identify paracrine factors.
Repeated I.T. injections of UCB-MSCs into APP/PS1 mice. | GDF-15 improves endogenous hippocampal neurogenesis and synaptic activity through CSF [36]. |
|
| Human UCB-MSCs | 5XFAD | Coculture of UCB-MSCs with primary hippocampal neurons under Aβ42 peptide treatment to identify paracrine factors.
Transplantation of hUCB-MSCs via I.C.V. route. | Mitigates Aβ42-induced synaptic dysfunction by regulating TSP-1 release [37]. |
|
| Human UCB-MSCs | Tg2576 | UCB-MSCs I.V. transplantation into Tg2576 mice. | Improves cognitive function
Attenuates oxidative stress
Promotes cell proliferation and newborn cell survival
Promotes neurons generating
Promotes hippocampal neurogenesis
Increases expression of Sirt1, BDNF, and SYN [38]. |
|
| Human UCB-MSCs | Tg2576 | UCB-MSCs I.V. transplantation combined with resveratrol into Tg2576 mice. | Better UCB-MSC engraftment in the hippocampus.
Improves learning and memory
Enhances neurogenesis
Alleviates neural apoptosis in the hippocampus [39]. |
|
| Human WJ-MSCs and UCB-MSCs | 5XFAD | Coculture of MSCs with SVZ-derived NSCs from 5XFAD mice. | Induces neuronal development and neurite outgrowth [40]. |
|
| Rat BM-MSCs | APP/PS1 | I.C.V. injection of BM-MSCs into APP/PS1 mice. | Improves cognitive impairment by ameliorating astrocytic inflammation as well as synaptogenesis by increasing the expression of microRNA-146a in hippocampus [41]. |
|
| Human BM-MSCs | APP/PS1 | Tail I.V. injection of BM-MSCs into APP/PS1 mice. | Reduced levels of IL-1, IL-2, TNF-α, and IFN-γ.
Regulates the expression of Aβ-related genes [42]. |
|
| Mouse BM-MSCs | 3xTg-AD | Evaluation of I.V. injected BM-MSCs using serial [18F] florbetaben PET into 3xTg-AD mice. | The reduction of β-amyloid deposits during BMSCs treatment could be confirmed by PET [43]. |
|
| Mouse BM-MSCs | 3 × Tg-AD | Infusion of 111In-labeled BM-MSCs via I.V. administration into 3 × Tg-AD mice. | The number of BM-MSCs reaching the brain is very small [44]. |
|
| Murine BM-MSCs | APP/PS1 | Injection of BM-MSCs into APP/PS1 mice via the tail vein. | Reduces pE3-Aβ plaque size.
Reduces gene expression of TNF-α, IL-6, MCP-1, and NGF.
Reduces microglial number and microglia size [45]. |
|
| Murine BM-MSCs | APP/PS1 | Single I.V. and repeated I.N. administration of secretome collected from MSCS exposed in vitro to AD mouse brain homogenates from APP/PS1 mouse. | A single infusion:
Transient memory recovery
Improves the inflammatory phenotype of astrocytes.
Reduces brain amyloidosis and microglial activation.
Repeated infusions:
Sustains memory recovery
Reduces neuroinflammation
Decreases brain amyloidosis
Increases neuronal density in both cortex and hippocampus
Diminishes hippocampal shrinkage [47]. |
|
| Human MenSCs | APP/PS1 | I.C. transplantation of MenSCs into an APP/PS1 mice. | Improves the spatial learning and memory
Mitigates amyloid plaques
Reduces tau hyperphosphorylation
Increases Aβ degrading enzymes
Modulates a panel of proinflammatory cytokines associated with an altered microglial phenotype [48]. |
|
| Rat AD-MSCs | APP/PS1 | Transplantation of AD-MSCs into the hippocampi of APP/PS1 mice with an automated infusion pump. | Reduces oxidative stress
Alleviates cognitive impairment
Promotes neurogenesis in the SGZ of the hippocampus
Increases the number of neuroblasts in the SVZ of the hippocampus [49]. |
|
| AM-MSCs | APP/PS1 | Intrahippocampal transplantation of AM-MSCs into APP/PS1 mice. | Reduced amyloid-β peptide
(Aβ) deposition and rescued spatial learning and memory
Reduced amyloid-β peptide
(Aβ) deposition and rescued spatial learning and memory
Improves the spatial learning and memory.
Reduces Aβ deposition
Intensifies release of Aβ degrading enzymes
Reduces microglia activation.
Increases hippocampal synaptic density and neurogenesis mediated by BDNF [50]. |
|
| MSC-EVs | 3xTg | Administration of EVs derived from cytokine-preconditioned MSCs through the I.N. route into 3xTg mice. | Decrease microglia activation.
Increases dendritic spine density [11]. |
|
| MSC-RVG-Exo | APP/PS1 mice | Use of RVG peptide to target I.V. infused MSC-Exo to the brain of transgenic APP/PS1 mice. | Improves cognitive function better than unmodified exosomes.
Decrease plaque deposition and Aβ levels.
Reduces the activation of astrocytes.
Reduces the expression of proinflammatory mediators such as TNF-α, IL-β, and IL-6.
Raises the levels of IL-10, IL-4, and IL-13 [53]. |
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