Dataset Information

Resveratrol Preincubation Enhances the Therapeutic Efficacy of hUC-MSCs by Improving Cell Migration and Modulating Neuroinflammation Mediated by MAPK Signaling in a Mouse Model of Alzheimer's Disease.

ABSTRACT: Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) are promising for the treatment of Alzheimer's disease (AD). However, their low rate of migration and survival in the brain limit their clinical applicability. This study is designed to improve the therapeutic potential of hUC-MSCs by preincubating them with resveratrol, a natural polyphenol capable of regulating cell destiny. Herein, we demonstrate that resveratrol preincubation enhances the migration of hUC-MSCs in vitro, as well as their survival and homing into the hippocampus of AD mice in vivo. Moreover, resveratrol-primed MSCs were better able to inhibit amyloid-β peptide (Aβ) deposition, Tau hyperphosphorylation, and oxidative stress, all while improving learning and memory. Notably, we found that hUC-MSCs inhibited neuroinflammation by reacting with astrocytes and microglial cells and suppressing mitogen-activated protein kinases (MAPKs), extracellular signal kinases (ERK), p38 kinases (p38), and c-Jun N-terminal kinases (JNK) signaling pathways in the hippocampus of AD mice. Furthermore, resveratrol pretreatment enhanced these effects. Conclusively, the current study revealed that resveratrol preconditioning protected hUC-MSCs against the hostile microenvironment characteristic of AD and enhanced their viability and homing into the brain of AD mice. The use of resveratrol-pretreated hUC-MSCs is thereby proposed to be a promising therapy for AD.

SUBMITTER: Wang X

PROVIDER: S-EPMC7118399 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundHuman umbilical cord mesenchymal stem cells (hUC-MSCs) are widely used in cell therapy due to their robust immunomodulatory and tissue regenerative capabilities. Currently, the predominant method for obtaining hUC-MSCs for clinical use is through planar culture expansion, which presents several limitations. Specifically, continuous cell passaging can lead to cellular aging, susceptibility to contamination, and an absence of process monitoring and control, among other limitations. To overcome these challenges, the technology of microcarrier-bioreactor culture was developed with the aim of ensuring the therapeutic efficacy of cells while enabling large-scale expansion to meet clinical requirements. However, there is still a knowledge gap regarding the comparison of biological differences in cells obtained through different culture methods.MethodsWe developed a culture process for hUC-MSCs using self-made microcarrier and stirred bioreactor. This study systematically compares the biological properties of hUC-MSCs amplified through planar culture and microcarrier-bioreactor systems. Additionally, RNA-seq was employed to compare the differences in gene expression profiles between the two cultures, facilitating the identification of pathways and genes associated with cell aging.ResultsThe findings revealed that hUC-MSCs expanded on microcarriers exhibited a lower degree of cellular aging compared to those expanded through planar culture. Additionally, these microcarrier-expanded hUC-MSCs showed an enhanced proliferation capacity and a reduced number of cells in the cell cycle retardation period. Moreover, bioreactor-cultured cells differ significantly from planar cultures in the expression of genes associated with the cytoskeleton and extracellular matrix.ConclusionsThe results of this study demonstrate that our microcarrier-bioreactor culture method enhances the proliferation efficiency of hUC-MSCs. Moreover, this culture method exhibits the potential to delay the process of cell aging while preserving the essential stem cell properties of hUC-MSCs.

Dataset Information

Resveratrol Preincubation Enhances the Therapeutic Efficacy of hUC-MSCs by Improving Cell Migration and Modulating Neuroinflammation Mediated by MAPK Signaling in a Mouse Model of Alzheimer's Disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets