Intranasal delivery of human Wharton's jelly-derived mesenchymal stem cells alleviates Aβ-induced Alzheimer's symptoms in rat models by regulating neurotrophic and apoptotic factors.

Alzheimer's disease (AD) is the most common cause of dementia in adulthood, followed by cognitive and behavioral deficits. Today, mesenchymal stem cell (MSC)-based therapy is a suitable therapeutic option to improve regenerative medicine approaches against neurodegenerative disorders, including AD. This study aimed to investigate the effects of human Wharton's jelly-derived MSCs (WJ-MSCs) on AD-like rat models (rats treated with amyloid beta 1-42 (Aβ_1-42)) by evaluating the expression of neurotrophic factors such as brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), as well as the expression of apoptotic factors such as B-cell lymphoma 2 (BCL2, an anti-apoptotic factor to inhibit apoptosis) and BCL2-associated X protein (BAX, a pro-apoptotic factor to regulate apoptosis). After treatment of AD rat models with WJ-MSCs, behavioral tests (i.e., passive avoidance and Morris water maze) showed cognitive improvements, and amelioration of cells in the CA1 area of the hippocampus was detected by cresyl violet staining. Additionally, real-time polymerase chain reaction (RT-PCR) of the hippocampus indicated an increase in the expression level of the BDNF, NGF, and BCL2 genes and a decrease in the expression level of the BAX gene. Overall, the WJ-MSCs improved the cognitive function in AD rat models by increasing the neurotrophic and anti-apoptotic factors and decreasing the pro-apoptotic factor. This graphical abstract depicts the process of isolating mesenchymal stem cells (MSCs) from human Wharton's jelly (WJ) and their subsequent use in an Alzheimer's disease (AD) rat model. The left side of the image illustrates the steps involved in isolating MSCs from WJ. The right side of the image shows how AD rat models are generated under stereotaxic injection of Aβ. In the middle, intranasally administration of MSCs is shown and then how their effects are evaluated using behavioral tests, nissl staining, and RT-qPCR. [ABSTRACT FROM AUTHOR]