Effect of Multiple Intraperitoneal Injections of Human Bone Marrow Mesenchymal Stem Cells on Cuprizone Model of Multiple Sclerosis

Abstract

Background:Bone marrow mesenchymal stem cells (BM-MSCs) elicit neuroprotective effects, and their repair ability has been investigated in different experimental models. We aimed to investigate the effect of multiple i.p. BM-MSCs injections in the cuprizone model of multiple sclerosis in mice.Methods:Adult male C57BL/6 mice (n = 40) were fed a regular diet or a diet containing cuprizone (0.2% w/w) for six weeks. Bone marrow samples were taken from patients with spinal cord injury. BM-MSCs (2 × 106 in 1 milliliter medium) were administered intraperitoneally for two consecutive weeks at the end of the forth weeks of cuprizone administration. Animals (n = 12) were perfused with 10% paraformaldehyde at the end of sixth week. The brains were sectioned coronally in 6-8-μm thickness (-2.3 to 1.8 mm from bregma). The sections were stained by luxol fast blue-cresyl violet, and images were captured via a microscope. Demyelination ratio was estimated in corpus callosum in a blind manner. A quantitative real-time PCR was used to measure the myelin basic protein gene expression at sixth week.Results:Histologically, cuprizone induced demyelination in the corpus callosum. Demyelinated area was diminished in the corpus callosum of cell-administered group. Cuprizone could decrease myelin-binding protein mRNAs expression in corpus callosum, which was significantly recovered after BM-MSCs injections.Conclusion:Our data indicated a remyelination potency of multiple i.p. BM-MSCs in the cuprizone model of multiple sclerosis in mice.

Exosome Treatment Enhances Anti-Inflammatory M2 Macrophages and Reduces Inflammation-Induced Pyroptosis in Doxorubicin-Induced Cardiomyopathy

“…Moreover, recent studies suggest that intraperitoneally (i.p.) transplanted stem cells or derived exosomes showed protection in cardiac and many other diseases [19,69,70,71,72,73] The current study uses i.p. injections to administer ESCs or ES-Exos and shows inhibition of pyroptosis and adverse cardiac remodeling in DIC.…”

Cell‐based experimental strategies for myelin repair in multiple sclerosis

“…Cell-treated animals showed reduced demyelination and astrogliosis, attenuated loss of OCs and improved remyelination, compared to vehicle-treated cuprizone group. The authors also found that some transplanted BM-MSCs could penetrate the blood-brain barrier in this non-immune model and few of them were found to express GFAP.The beneficial effects of MSCs in the cuprizone MS model were mainly linked to the induction of endogenous restorative effects without differentiation of transplanted cells into remyelinating OCs(El-Akabawy & Rashed, 2015;Hedayatpour et al, 2013; Jaramillo- Merchan et al, 2013;Marzban et al, 2018). In most cases, MSCs were…”

“…The beneficial effects of MSCs in the cuprizone MS model were mainly linked to the induction of endogenous restorative effects without differentiation of transplanted cells into remyelinating OCs (El‐Akabawy & Rashed, 2015; Hedayatpour et al, 2013; Jaramillo‐Merchan et al, 2013; Marzban et al, 2018). In most cases, MSCs were shown not to cross the blood–brain barrier, which remains intact in this model (Nessler et al, 2013; Salinas Tejedor et al, 2015).…”

Mesenchymal Stem Cells in Multiple Sclerosis: Recent Evidence from Pre-Clinical to Clinical Studies

“…Multiple BM-MSCs intraperitoneal injections were also able to reduce demyelination in the corpus callosum and an increased expression of MBP was found. However, BM-MSCs were not detected inside the corpus callosum [ 33 ]. Instead, BM-MSCs administered intravenously were able to migrate and engraft in the brain, where they reduced demyelination and enhanced remyelination in the corpus callosum.…”