Preconditioning adipose-derived mesenchymal stem cells with dimethyl fumarate promotes their therapeutic efficacy in the brain tissues of rats with Alzheimer's disease

Hossein Babaei; Alireza Kheirollah; Mina Ranjbaran; Maryam Cheraghzadeh; Alireza Sarkaki; Maryam Adelipour

doi:10.1016/j.bbrc.2023.06.045

Preconditioning adipose-derived mesenchymal stem cells with dimethyl fumarate promotes their therapeutic efficacy in the brain tissues of rats with Alzheimer's disease

Biochem Biophys Res Commun. 2023 Sep 10:672:120-127. doi: 10.1016/j.bbrc.2023.06.045. Epub 2023 Jun 15.

Authors

Hossein Babaei¹, Alireza Kheirollah², Mina Ranjbaran³, Maryam Cheraghzadeh¹, Alireza Sarkaki⁴, Maryam Adelipour⁵

Affiliations

¹ Department of Clinical Biochemistry, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; Persian Gulf Physiology Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
² Department of Clinical Biochemistry, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
³ Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
⁴ Medical Plant Research Center, Ahvaz Jundishapur University of Medical Science, Ahvaz, Iran; Persian Gulf Physiology Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. Electronic address: sarkaki_a@ajums.ac.ir.
⁵ Department of Clinical Biochemistry, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; Persian Gulf Physiology Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. Electronic address: adelipour-m@ajums.ac.ir.

PMID: 37348174
DOI: 10.1016/j.bbrc.2023.06.045

Abstract

Aim: Transplantation of mesenchymal stem cell (MSC) has been suggested to be a promising method for treating neurodegenerative conditions, including Alzheimer's disease (AD). However, the poor survival rate of transplanted MSCs has limited their therapeutic application. This study aimed to evaluate whether preconditioning MSCs with dimethyl fumarate (DMF), a Nrf2 inducer, could enhance MSC therapeutic efficacy in an amyloid-β (Aβ_1-42)-induced AD rat model.

Methods: The survival and antioxidant capacity of MSCs treated with DMF were assessed in vitro. Aβ_1-42 intrahippocampal injection was used to create a rat model of AD. Following the transplantation of MSCs preconditioned with DMF and using the Morris blue maze test, spatial learning and memory were assessed. Using RT-qPCR, we evaluated the gene expression related to apoptosis and neurotrophins in the hippocampus region.

Results: Treatment with DMF enhanced cell survival and Nrf2 protein expression in MSCs in vitro. Preconditioning with DMF also enhanced the efficacy of transplanted MSCs in rescuing learning and spatial memory deficits in Aβ-AD rats. Besides, DMF preconditioning enhanced the neuroprotective effect of transplanted MSCs in the hippocampus of rats treated with Aβ_1-42 by decreasing the expression of apoptotic markers (Bax, caspase 3, and cytochrome c), and elevating the expression of the anti-apoptotic marker Bcl2 and neurotrophins, including BDNF and NGF.

Conclusion: Preconditioning MSCs with DMF boosted the therapeutic efficacy of these cells; therefore, it could serve as a targeted strategy for increasing the therapeutic efficacy of MSCs in treating neurodegenerative disorders, including AD.

Keywords: Alzheimer's disease; Apoptosis; DMF; MSC; Neurotrophic factor; Preconditioning.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease* / genetics
Animals
Brain / metabolism
Dimethyl Fumarate / pharmacology
Disease Models, Animal
Mesenchymal Stem Cell Transplantation* / methods
Mesenchymal Stem Cells* / metabolism
NF-E2-Related Factor 2 / metabolism
Nerve Growth Factors / metabolism
Rats
Spatial Memory

Substances

Dimethyl Fumarate
NF-E2-Related Factor 2
Nerve Growth Factors