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

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.

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.

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-α, 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.

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.