Fe3O4@Polydopamine Nanoparticle-Loaded Human Umbilical Cord Mesenchymal Stem Cells Improve the Cognitive Function in Alzheimer's Disease Mice by Promoting Hippocampal Neurogenesis

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.