Faculty Opinions recommendation of Human umbilical cord mesenchymal stem cells transplantation improves cognitive function in Alzheimer's disease mice by decreasing oxidative stress and promoting hippocampal neurogenesis.

Author(s):  
Filippo Milano
2020 ◽  
Author(s):  
Yuxiang Wang ◽  
Jinlan Jiang ◽  
Xueqi Fu ◽  
Jingtian Zhang ◽  
Jiayue Song ◽  
...  

Abstract BackgroundOne of the most promising treatments for neurodegenerative diseases is the stem cell therapy; however, there are still some limitations in the treatment of Alzheimer's disease (AD), and the specific molecular mechanism that affects the cognitive function remains unclear. Therefore, it is necessary to develop a strategy to increase the recruitment of stem cells to the lesion site for clinical application. Fe3O4 nanoparticles have good physiological stability, biocompatibility, and is conducive to the active uptake of stem cells.MethodsIn this study, superparamagnetic iron oxide nanoparticles composed of magnetic Fe3O4 and polydopamine (PDA) shells were used to label human umbilical cord mesenchymal stem cells (hUC-MSCs) in order to increase the targeting of hUC-MSCs. We first detected the effect of Fe3O4 nanoparticles on the proliferation and differentiation of hUC-MSCs, and identified the distribution of Fe3O4@PDA labeled hUC-MSCs in APP/PS1 transgenic mice. We also determined the effects of hUC-MSCs on OA-induced apoptosis in vitro, and Fe3O4@PDA labeled hUC-MSCs on the cognitive function of AD mice by water maze test. The effects of Fe3O4@PDA labeled hUC-MSCs on related-proteins in hippocampus of AD mice were determined by WB and immunohistochemistry.ResultsFe3O4@PDA labeling did not affect the biological characteristics of hUC-MSCs, but did increase the efficiency of hUC-MSCs entering the brain. Moreover, the results of the water maze test showed that compared with single hUC-MSCs, Fe3O4@PDA-labeled hUC-MSCs improved the cognitive ability of APP/PS1 transgenic mice more significantly. Other experimental data, including WB, immunohistochemistry, showed that the expression of essential proteins in the hippocampus, such as amyloid precursor protein (App), synaptophysin (SYN), brain-derivedneurotrophic factor (BDNF), glial fibrillary acidic protein (GFAP), etc., are affected by Fe3O4@PDA coated-hUC-MSCs. The study showed a well-established Aβ deposition by promoting neurogenesis and synaptic plasticity and increased protein levels of BDNF, SYN, and GFAP.ConclusionFe3O4@PDA is a promising magnetic nanomaterial, which can increase the targeting of stem cells. The regulation of hUC-MSCs could improve the memory and cognitive ability of AD mice byexcessive generation of neuroprotective factors, which might be considered a viable therapy to treat AD.


2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Dian Li ◽  
Dan Zhang ◽  
Bo Tang ◽  
Yue Zhou ◽  
Wenhao Guo ◽  
...  

Objective. To investigate whether exosomes from human umbilical cord mesenchymal stem cells (hUC-MSCs) can protect against the toxic effects of oxalate and calcium oxalate monohydrate (COM) crystals in human proximal tubular epithelial (HK-2) cells. Methods. Exosomes were isolated from hUC-MSCs, purified by ultracentrifugation, and verified by examination of cell morphology using transmission electron microscopy and the presence of specific biomarkers. HK-2 cells received 1 of 4 treatments: control (cells alone), hUC-MSC exosomes, oxalate+COM, or oxalate+COM and hUC-MSC exosomes. Cell viability was determined using the MTT assay. Oxidative stress was determined by measuring LDH activity and the levels of H2O2, malondialdehyde (MDA), and reactive oxygen species (ROS). Expressions of N-cadherin, TGF-β, and ZO-1 were determined by immunofluorescence. Expressions of epithelial markers, mesenchymal markers, and related signaling pathway proteins were determined by western blotting. Results. After 48 h, cells in the oxalate+COM group lost their adhesion, appeared long, spindle-shaped, and scattered, and the number of cells had significantly decreased. The oxalate+COM treatment also upregulated TGF-β and mesenchymal markers, downregulated epithelial markers, increased the levels of LDH, H2O2, MDA, and ROS, decreased cell viability, and increased cell migration. The isolated exosomes had double-layer membranes, had hollow, circular, or elliptical shapes, had diameters mostly between 30 and 100 nm, and expressed CD9, CD63, and Alix. Treatment of HK-2 cells with hUC-MSC exosomes reversed or partly reversed all the effects of oxalate+COM. Conclusions. Exosomes from hUC-MSCs alleviate the oxidative injury and the epithelial-mesenchymal transformation of HK-2 cells that is induced by oxalate+COM.


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