Impact of Intraventricular Human Adipose-Derived Stem Cells Transplantation with Pregnenolone Treatment on Remyelination of Corpus Callosum in A Rat Model of Multiple Sclerosis

Abstract

Objective: Multiple sclerosis (MS) is known as a nerve tissue disorder, which causes demyelination of central nervous system (CNS) fibers. Cell-based treatment is a novel strategy for the treatment of demyelinating diseases such as MS. Adipose-derived stem cells (ADSCs) have neuroprotective and neuroregenerative effects and pregnenolone as a neurosteroid has remarkable roles in neurogenesis. We intend to examine the impact of intraventricular transplantation of human ADSCs and systemic injection of pregnenolone on the remyelination of a rat model cuprizone-induced demyelination.Materials and Methods: This experimental study was performed on 36 male Wistar rats that received a regular diet and a cuprizone diet for 3 weeks for M.S. induction. Through lipoaspirate surgery, human-ADSCs (hADSCs) were obtained from a patient. Six groups of rats (n=6): healthy, MS, sham, pregnenolone injection, ADSCs transplantation, and pregnenolone injection/ADSCs transplantation were included in this study. For assessment of remyelination, transmission electron microscopy (TEM), immunohistochemistry staining, real-time reverse transcription-polymerase chain reaction (RT-PCR), and enzyme-linked immunosorbent assay (ELISA) were performed.Results: TEM outcomes revealed an increase in the thickness of the fibers myelin in the treatment groups (P<0.05). We also observed a significant upregulation of MBP, PDGFR-alpha, and MOG after treatment with hADSCs and pregnenolone compared to other study groups (P<0.001). These results were confirmed by immunostaining analysis. Moreover, there was no significant difference between the ADSCs/pregnenolone group and the control group regarding the level of MBP, A2B5, and MOG proteins in ELISA.Conclusion: Our data implied that the remyelination and cell recovery were more improved by intraventricular ADSCs transplantation and pregnenolone injection after inducing a rat model of MS.