Retinoic acid-treated human umbilical cord-derived mesenchymal stem cells attenuate Alzheimer’s disease in an animal model

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder marked by the accumulation of Aβ plaques and neurofibrillary tangles, leading to cognitive decline. Current therapeutic options provide only symptomatic relief and do not correct the underlying disease process. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) and retinoic acid (RA) have shown potential in promoting neuronal regeneration. Although RA-treated MSCs have been reported to enhance neuronal differentiation, their effects on AD-associated molecular changes and functional outcomes have not been fully investigated. This study aimed to evaluate the effects of RA-treated hUC-MSCs on AD-associated pathological and functional changes in a mouse model of Alzheimer’s disease. RA-treated hUC-MSCs were administered to a streptozotocin (STZ)-induced mouse model of Alzheimer’s disease. All experimental groups were assessed for cognitive function, histopathological changes, expression of AD-associated genes, and APP protein expression. Mice receiving RA-treated hUC-MSCs showed improved spatial memory and neuronal morphology. In addition, RA-treated hUC-MSCs significantly modulated the expression of AD-associated genes, including IDE (P < 0.01) , APP (P < 0.01) , PSEN1 (P < 0.01) , PSEN2 (P < 0.01) , and APOE4 (P < 0.001) , along with a significant reduction in APP protein expression (P < 0.001). It can be concluded that RA pretreatment is a novel preconditioning strategy that improves the therapeutic potential of hUC-MSCs by improving cognitive function and modulating AD-associated pathological and molecular changes in the STZ-induced mouse model.