Adipose Tissue-Derived Mesenchymal Stem Cells Alter Metabolites of Brain Cholesterol Homeostasis in An Alzheimer’s Model

Document Type : Original Article


1 Department of Clinical Biochemistry, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

2 Cellular and Molecular Research Center, Medical Basic Sciencec Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

3 Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

4 Sirjan School of Medical Sciences, Sirjan, Iran

5 Surgery Department, Geisel School of Medicine at Dartmouth, Hanover, NH, United States

6 Department of Physiology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

7 Persian Gulf Physiology Research Centre, Basic Medical Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

8 Atherosclerosis Research Centre, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran


Objective: Disruption of cholesterol homeostasis in Alzheimer’s disease (AD) plays a crucial role in disease
pathogenesis, making it a potential therapeutic target. Mesenchymal stem cells (MSCs) show promise in treating
cognitive impairment and provide a novel therapeutic approach. This study aims to investigate the effects of MSCs on
specific metabolites associated with brain cholesterol homeostasis in an AD rat model.
Materials and Methods: In this experimental study, animals were divided into three groups: control, AD, and
AD+MSCs. AD was induced using amyloid beta (Aβ) and confirmed through the Morris water maze (MWM) behavioural
test and Congo red staining. MSCs were extracted, characterised via flow cytometry, subjected to osteoblast and
adipose differentiation, and injected intraventricularly. The cholesterol metabolite levels were measured using gas
chromatography-mass spectrometry (GC)-MS and compared among the groups.
Results: Treatment with MSCs significantly improved memory function in the AD+MSCs group compared to the
AD group and the number of beta-amyloid plaques decreased according to histological assessment. Disturbances
in the brain cholesterol metabolites that included desmosterol, 7-dehydrocholesterol, 24S-hydroxycholesterol,
27-hydroxycholesterol and cholesterol were observed in the AD group compared to the control group. Treatment with
MSCs resulted in significant alterations in the levels of these metabolites.
Conclusion: The findings indicate that MSC therapy has the potential to improve AD by modulating brain cholesterol
homeostasis and promoting the differentiation of stem cells into nerve cells. The results emphasize the importance of
investigating the role of cholesterol metabolites in the context of MSC therapy to gain deeper insights into underlying
mechanisms of the therapeutic efficacy of MSCs in AD.


Main Subjects

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