Abstract
Purpose: Promising advances have been made in mesenchymal stem cell transplantation to reinducethe immune tolerance in neuroinflammatory animal models and multiple sclerosis (MS)patients. The available evidence demonstrated that immunomodulatory effects of mesenchymalstem cell are particularly exerted through releasing exosomes to their environment. Wetherefore, aimed to comparatively assess the potential effect of mesenchymal stem cells andmesenchymal stem cells-derived exosomes on proliferation and function of the CD4+CD25− conventional T cells, isolated from relapsing-remitting MS patients. Methods: Mesenchymal stem cells were isolated from human umbilical cord tissues and usedfor exosome isolation via ultracentrifugation. Both mesenchymal stem cells and mesenchymalstem cells-derived exosomes were evaluated for their anti-inflammatory effects againstthe proliferation of T cells isolated from two groups of individuals in vitro, MS patients andhealthy subjects. Cytokine production of conventional T cells (interferon-γ, interleukin-10, andinterleukin-17) was also assessed, using flow cytometry for the patients and healthy individuals. Results: Here, evidence shows that MSCs and MSC-derived exosomes dampen proliferationand percentage of conventional T cells that produce IFN-γ (healthy control: P < 0.001) andinterleukin-17 (healthy control: P <0.001, MS patients: P < 0.001), with a significant increaseof IL-10 producing cells in the patients and healthy individuals. Surprisingly, MSC-derivedexosomes demonstrated higher immune-modulating properties on conventional T cellsresponses, compared to mesenchymal stem cells (MSCs). Conclusion: The current study, provides a novel approach of exocytosis on autoimmune therapy.In particular, Mesenchymal stem cell -derived exosomes, which are cell-derived biologics,could be considered as an alternative for Mesenchymal stem cells in treating MS.
Highlights
Multiple sclerosis (MS) is a demyelinating autoimmune disorder of the central nervous system (CNS), where abnormal activation of autoreactive T cells leads to neurodegeneration 1
10 n they are able to pass through boundaries like blood-brain barrier (BBB) 11; mesenchymal stem cells (MSCs)-derived exosomes attracted attention to be used for the treatment of multiple a sclerosis in several animal studies
The spindle-shaped cells were adherent to the cell culture flasks, capable of differentiating into the osteogenic as well as adipogenic cell lineage which is demonstrated by intracellular accumulation of calcium and lipid vacuoles, respectively
Summary
Mesenchymal stem cells were isolated from human umbilical cord tissues and used for exosome isolation via ultracentrifugation. Both mesenchymal stem cells and mesenchymal stem cells-derived exosomes were evaluated for their antiinflammatory effects against the proliferation of T cells isolated from two groups of individuals in vitro, MS patients and healthy subjects. T Results: Here, evidence shows that MSCs and MSC-derived exosomes dampen proliferation and percentage of conventional T cells that produce IFN-γ (healthy ip control: p
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